American biochemist
Kevin Struhl (born September 2, 1952) is an American
molecular biologist and the David Wesley Gaiser Professor of Biological Chemistry and Molecular Pharmacology at
Harvard Medical School .
[1] Struhl is primarily known for his work on
transcriptional regulatory mechanisms in
yeast using molecular, genetic, biochemical, and genomic approaches.
[2] More recently, he has used related approaches to study
transcriptional regulatory circuits involved in
cellular transformation and the formation of
cancer stem cells .
Early life and education
Kevin Struhl was born on September 2, 1952, in
Brooklyn , New York. His father, Joseph Struhl (1921-2008), was an entrepreneur who put up some of the first indoor tennis courts.
[3]
[4] His mother, Harriet Schachter Struhl (1927-) was a
psychologist . He has 3 younger brothers,
Gary (1954-), a developmental
geneticist at
Columbia Medical School , Clifford (1956-) who took over the family business, and Steven (1958-) an
orthopedic surgeon .
[5] The Struhl family moved to
Great Neck, NY in 1956, where Struhl graduated from
Great Neck South high school in 1970. Struhl and his father were once ranked #3 in father-son tennis in the Eastern section of the
United States Tennis Association . Struhl completed his S.B and S.M. in biology in 1974 with
Boris Magasanik from the
Massachusetts Institute of Technology . He obtained his Ph.D. in 1979 with
Ronald W. Davis at
Stanford Medical School and then spent two years as a postdoctoral fellow with
Sydney Brenner at the
Laboratory of Molecular Biology at the
Medical Research Council in
Cambridge, UK .
Career and Research
Recombinant DNA technology, yeast molecular biology, and reverse genetics
As a graduate student, Struhl cloned and functionally expressed the first eukaryotic protein-coding gene in
E.coli , a landmark in recombinant DNA technology.
[6]
[7] Cloned yeast genes were essential for
Gerald Fink to develop transformation methods that Struhl used to co-discover
DNA replication origins
[8]
[9] and to create the first vectors for molecular genetic manipulations in yeast.
[8] Struhl was among the first to use “reverse genetic” analysis; i.e., making mutations in cloned genes, introducing the mutated derivatives back into cells, and assessing the resulting phenotypes.
[10]
Structure and function of eukaryotic promoters: the yeast his3 paradigm
Using “reverse genetics” to study gene regulation in vivo , Struhl generated the first eukaryotic promoter mutants and performed a detailed analysis of the his3 gene. This resulted in early descriptions of all the basic types of gene-regulatory elements: upstream elements that act a distance from the promoter;
[11]
[10] regulatory sites that activate gene expression in specific conditions;
[12] poly(dA:dT) sequences;
[13] functionally distinct TATA elements;
[14]
[15] initiator elements;
[16] repression sequences that act upstream of and at a distance from promoters.
[17]
Structure and function of a transcriptional activator, the yeast Gcn4 paradigm
Struhl invented “reverse biochemistry”, the use of in vitro synthesized proteins to identify DNA-binding transcription factors and study protein-DNA interactions.
[18] In one of the first examples of a eukaryotic sequence-specific binding protein, he discovered that Gcn4 coordinately activates many genes involved in amino acid biosynthesis by direct binding to bound target sites in their promoters.
[18] He developed the first “random selection” method for DNA target sites (and other genetic elements) from random-sequence oligonucleotides.
[19] He showed that Gcn4 binds as a dimer
[20] via its leucine zipper,
[21] described how it recognizes target sites at atomic resolution,
[22] and showed that the Gcn4 binding surface folds when bound to its target site, the first example of an “induced fit” model for DNA binding.
[23] Detailed genetic dissection led to the discovery of short acidic activation domains required for transcription that are functionally autonomous and can be encoded by different sequences.
[24]
[25] Lastly, Struhl showed that the Jun oncogene encodes a Gcn4 homolog that binds the same sequences
[26] and activates transcription in yeast cells.
[27] Jun was the first example of an oncogene that encodes a transcription factor.
Transcriptional regulatory mechanisms
Using T7 RNA polymerase in yeast cells, Struhl demonstrated distinct chromatin-accessibility and protein-protein interaction mechanisms for transcriptional activation.
[28] Novel genetic approaches - altered-specificity mutants,
[29] protein fusions for artificial recruitment
[30]
[31] - along with chromatin immunoprecipitation (ChIP), demonstrated that transcriptional regulation in yeast occurs primarily at the level of recruitment of the RNA polymerase II transcription machinery.
[32] Struhl showed that the TATA-binding protein is required for transcription by all 3 nuclear RNA polymerases
[33] and defined a surface required specifically for transcription by RNA polymerase III.
[34] Together with Tom Gingeras, he used tiled microarrays to generate the first unbiased, genome-scale analysis of transcription factor binding in mammalian cells, leading to the discovery of far more transcription binding sites in vivo than predicted, including many that control non-coding RNAs.
[35]
[36] His contributions in diverse areas of transcriptional regulation include mechanistic roles of general factors for transcriptional initiation,
[37]
[38]
[39]
[40] promoter directionality,
[41] high level of transcriptional noise due to infidelity of Pol II initiation,
[42] role of TAFs
[43]
[44]
[45] and Mediator
[46]
[47] in transcriptional activation, coordinate regulation of ribosomal protein genes in response to growth and stress signals,
[48]
[49] repression by the Cyc8-Tup co-repressor complex that controls numerous stress pathways,
[50]
[51] the response to osmotic stress
[52] including the discovery of a pre-transcriptional response,
[53] transcriptional elongation,
[54]
[55] 3’ end formation,
[55]
[56] and mRNA stability.
[57]
[58] Lastly, Struhl was among the first to use ChIP to analyze transcription in E. coli , showing that the transition between initiation and elongation is highly variable and often rate-limiting
[59] and uncovering extensive functional overlap between sigma factors.
[60]
Role of chromatin in transcription and DNA replication
Struhl’s work on the role of chromatin in transcriptional regulation include initial descriptions of 1) a DNA sequence, poly(dA:dT), that activates transcription via its intrinsic effect on nucleosome stability,
[61]
[62] 2) mechanistic principles for how the nucleosome positioning pattern occurs in vivo ,
[63]
[64] 3) transcriptional repression via targeted recruitment of a histone deacetylase,
[65]
[66] 4) molecular memory of recent transcriptional activity via targeted histone methylation via recruitment by elongating Pol II,
[67] 5) dynamic eviction and re-association of histones during transcriptional elongation,
[68] and 6) methylation of lysine 79 within the histone H3 core
[69] and a model for position-effect variegation.
[70] With respect to DNA replication, Struhl demonstrated that a histone acetylase (HBO1) is both a transcriptional co-activator and a co-activator for the Cdt1 replication licensing factor
[71]
[72] that coordinates the transcriptional and DNA replication response to non-genotoxic stress.
[73] In addition, he showed that the DNA origin replication complex (ORC) selectively binds regions with a specific chromatin pattern, and that the location of ORC binding sites plays a major role in DNA replication timing.
[74]
An epigenetic switch linking inflammation to cancer
Struhl discovered an epigenetic switch from non-transformed to transformed cells, a new type of step in cancer progression distinct from mutation or DNA methylation.
[75] This epigenetic switch is mediated by a positive inflammatory feedback loop that involves the joint role of the NF-kB, STAT3, AP-1, and TEAD transcription factors along with YAP/TAZ co-activators as well as Let7 and other microRNAs.
[76]
[77]
[78] He also uncovered a dynamic equilibrium between cancer stem cells and non-stem cancer cells mediated by interleukin 6
[79] and defined the transcriptional circuit mediating the biphasic switch between these physiological states.
[80]
[81]
Anti-cancer and anti-inflammatory properties of metformin
Struhl showed that metformin, the first-line drug for treating type 2 diabetes, selectively kills cancer stem cells and acts together with chemotherapy to inhibit tumor progression and prolong remission.
[82]
[83] Metformin exerts its effects on cellular transformation and cancer stem cell growth via its inhibitory effect on the inflammatory pathway.
[84]
Awards
References
^ Chandler, Courtney (2022-12-02).
" 'Independent agents' no more" . American Society for Biochemistry and Molecular Biology .
^ Struhl, Kevin (1995).
"Yeast Transcriptional Regulatory Mechanisms" . Annual Review of Genetics . 29 : 651–674.
doi :
10.1146/annurev.ge.29.120195.003251 .
PMID
8825489 .
^ Horn, Houston (1965-03-08).
"As Long As There's A Place To Go, Let It Snow" . Sports Illustrated .
^ Friedman, Charles (1964-11-22).
"$400,000 Indoor Tennis Center With 4 Clay Courts Opens Here" (PDF) . The New York Times .
^
"Dr. Steven Struhl NYC Orthopedic Surgeon" . Shoulders & Knees Steven Struhl MD .
^ Struhl, K; Davis, RW (1977-12-01).
"Production of a functional eukaryotic enzyme in Escherichia coli: cloning and expression of the yeast structural gene for imidazole-glycerolphosphate dehydratase (his3)" . PNAS . 74 (12): 5255–5259.
Bibcode :
1977PNAS...74.5255S .
doi :
10.1073/pnas.74.12.5255 .
PMC
431671 .
PMID
341150 .
^ Struhl, K; Cameron, JR; Davis, RW (1976-05-01).
"Functional genetic expression of eukaryotic DNA in Escherichia coli" . PNAS . 73 (5): 1471–1475.
Bibcode :
1976PNAS...73.1471S .
doi :
10.1073/pnas.73.5.1471 .
PMC
430318 .
PMID
775490 .
^
a
b Struhl, K; Stinchcomb, DT; Scherer, S; Davis, RW (1979-03-01).
"High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules" . PNAS . 76 (3): 1035–1039.
Bibcode :
1979PNAS...76.1035S .
doi :
10.1073/pnas.76.3.1035 .
PMC
383183 .
PMID
375221 .
^ Stinchcomb, DT; Struhl, K; Davis, RW (1979-11-01).
"Isolation and characterization of a yeast chromosomal replicator" . Nature . 282 (5734): 39–43.
Bibcode :
1979Natur.282...39S .
doi :
10.1038/282039a0 .
PMID
388229 .
S2CID
4326901 .
^
a
b Struhl, Kevin (1979). "The yeast his3 gene". Biochemistry .
^ Struhl, Kevin (1981-07-01).
"Deletion mapping a eukaryotic promoter" . PNAS . 78 (7): 4461–4465.
Bibcode :
1981PNAS...78.4461S .
doi :
10.1073/pnas.78.7.4461 .
PMC
319811 .
PMID
7027262 .
^ Struhl, Kevin (1982-11-18).
"Regulatory sites for his3 expression in yeast" . Nature . 300 (5889): 285–286.
doi :
10.1038/300284a0 .
PMID
6755264 .
S2CID
4308484 .
^ Struhl, Kevin (1985-12-01).
"Naturally occurring poly(dA-dT) sequences are upstream promoter elements for constitutive transcription in yeast" . PNAS . 82 (24): 8419–8423.
Bibcode :
1985PNAS...82.8419S .
doi :
10.1073/pnas.82.24.8419 .
PMC
390927 .
PMID
3909145 .
^ Chen, W; Struhl, K (1988-04-01).
"Saturation mutagenesis of a yeast his3 TATA element: genetic evidence for a specific TATA-binding protein" . PNAS . 85 (8): 2691–2695.
Bibcode :
1988PNAS...85.2691C .
doi :
10.1073/pnas.85.8.2691 .
PMC
280064 .
PMID
3282236 .
^ Struhl, Kevin (1986-05-29).
"Constitutive and inducible Saccharomyces cerevisiae promoters: evidence for two distinct molecular mechanisms" . Molecular and Cellular Biology . 6 (11): 3847–3853.
doi :
10.1128/mcb.6.11.3847-3853.1986 .
PMC
367147 .
PMID
3540601 .
^ Chen, W; Struhl, K (1985-12-01).
"Yeast mRNA initiation sites are determined primarily by specific sequences, not by the distance from the TATA element" . The EMBO Journal . 4 (12): 3273–3280.
doi :
10.1002/j.1460-2075.1985.tb04077.x .
PMC
554654 .
PMID
3912167 .
^ Struhl, Kevin (1985-10-01).
"Negative control at a distance mediates catabolite repression in yeast" . Nature . 317 (6040): 822–824.
Bibcode :
1985Natur.317..822S .
doi :
10.1038/317822a0 .
PMID
3903516 .
S2CID
2404872 .
^
a
b Hope, IA; Struhl, K (November 1988).
"GCN4 protein, synthesized in vitro, binds to HIS3 regulatory sequences: implications for the general control of amino acid biosynthetic genes in yeast" . Cell . 43 (1): 177–188.
doi :
10.1016/0092-8674(85)90022-4 .
PMID
3907851 .
S2CID
22627291 .
^ Oliphant, AR; Brandl, CJ; Struhl, K (1989-07-01).
"Defining sequence specificity of DNA-binding proteins by selecting binding sites from random-sequence oligonucleotides: Analysis of the yeast GCN4 protein" . Molecular and Cellular Biology . 9 (7): 2944–2949.
doi :
10.1128/mcb.9.7.2944-2949.1989 .
PMC
362762 .
PMID
2674675 .
^ Hope, IA; Struhl, K (1987-09-01).
"GCN4, a eukaryotic transcriptional activator protein, binds as a dimer to target DNA" . The EMBO Journal . 6 (9): 2781–2784.
doi :
10.1002/j.1460-2075.1987.tb02573.x .
PMC
553703 .
PMID
3678204 .
^
^ Ellenberger, Thomas E; Brandl, Christopher J; Struhl, Kevin; Harrison, Stephen C (1992-12-24).
"The GCN4 basic-region-leucine zipper binds DNA as a dimer of uninterrupted a-helices: crystal structure of the protein-DNA complex" . Cell . 71 (7): 1223–1237.
doi :
10.1016/S0092-8674(05)80070-4 .
PMID
1473154 .
S2CID
13548424 .
^ Weiss, Michael A; Ellenberger, Thomas; Wobbe, C Richard; Lee, Jonathan P; Harrison, Stephen C; Struhl, Kevin (1990).
"Folding transition in the DNA-binding domain of GCN4 on specific binding to DNA" . Nature . 347 (6293): 575–578.
Bibcode :
1990Natur.347..575W .
doi :
10.1038/347575a0 .
PMID
2145515 .
S2CID
4366430 .
^ Hope, IA; Struhl, K (1986-09-12).
"Functional dissection of a eukaryotic transcriptional activator protein, GCN4 of yeast" . Cell . 46 (6): 885–894.
doi :
10.1016/0092-8674(86)90070-X .
PMID
3530496 .
S2CID
40730692 .
^ Hope, IA; Mahadevan, S; Struhl, K (1988-06-16).
"Structural and functional characterization of the short acidic transcriptional activation region of yeast GCN4 protein" . Nature . 333 (6174): 635–640.
Bibcode :
1988Natur.333..635H .
doi :
10.1038/333635a0 .
PMID
3287180 .
S2CID
2635634 .
^ Struhl, Kevin (1987-09-11).
"The DNA-binding domains of the jun oncoprotein and the yeast GCN4 transcriptional activator are functionally homologous" . Cell . 50 (6): 841–846.
doi :
10.1016/0092-8674(87)90511-3 .
PMID
3040261 .
S2CID
29588878 .
^ Struhl, Kevin (1988-04-14).
"The JUN oncoprotein, a vertebrate transcription factor, activates transcription in yeast" . Nature . 332 (6165): 649–650.
Bibcode :
1988Natur.332..649S .
doi :
10.1038/332649a0 .
PMID
3128739 .
S2CID
4350206 .
^ Chen, W; Tabor, S; Struhl, K (1987-09-25).
"Distinguishing between mechanisms of eukaryotic transcriptional activation with bacteriophage T7 RNA polymerase" . Cell . 266 (5183): 280–282.
doi :
10.1126/science.7939664 .
PMID
7939664 .
^ Klein, C; Struhl, K (1994-10-19).
"Increased recruitment of TATA-binding protein to the promoter by transcriptional activation domains in vivo" . Science . 266 (5183): 280–282.
doi :
10.1126/science.7939664 .
PMID
7939664 .
^ Keaveney, M; Struhl, K (May 1998).
"Activator-mediated recruitment of the RNA polymerase II machinery is the predominant mechanism for transcriptional activation in yeast" . Molecular Cell . 1 (6): 917–924.
doi :
10.1016/S1097-2765(00)80091-X .
PMID
9660975 .
^ Chatterjee, S; Struhl, K (1995-04-27).
"Connecting a promoter-bound protein to TBP bypasses the need for a transcriptional activation domain" . Nature . 374 (6525): 820–822.
doi :
10.1038/374820a0 .
PMID
7723828 .
S2CID
4325887 .
^ Kuras, L; Struhl, K (1999-06-10).
"Binding of TBP to promoters in vivo is stimulated by activators and requires Pol II holoenzyme" . Nature . 399 (6736): 609–613.
doi :
10.1038/21239 .
PMID
10376605 .
S2CID
204993837 .
^ Cormack, BP; Struhl, K (1992-05-15).
"The TATA-binding protein is required for transcription by all three nuclear RNA polymerases in yeast cells" . Cell . 69 (4): 685–696.
doi :
10.1016/0092-8674(92)90232-2 .
PMID
1586947 .
S2CID
7419671 .
^ Cormack, BP; Struhl, K (1993-10-08).
"Regional codon randomization: defining a TATA-binding protein surface required for RNA polymerase III transcription" . Science . 262 (5131): 244–248.
doi :
10.1126/science.8211143 .
PMID
8211143 .
^ Cawley, S.; et al. (2004-02-20).
"Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of non-coding RNAs" . Cell . 116 (4): 499–509.
doi :
10.1016/S0092-8674(04)00127-8 .
PMID
14980218 .
S2CID
7793221 .
^ Yang, Annie; Zhu, Zhou; Kapranov, Philipp; McKeon, Frank; Church, George M; Gingeras, Thomas R; Struhl, Kevin (2006-11-17).
"Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells" . Molecular Cell . 24 (4): 593–602.
doi :
10.1016/j.molcel.2006.10.018 .
PMID
17188034 .
^ Stargell, LA; Struhl, K (1995-07-07).
"The TBP-TFIIA interaction in the response to acidic activators in vivo" . Science . 269 (5220): 75–78.
doi :
10.1126/science.7604282 .
PMID
7604282 .
^ Lee, M; Struhl, K (1995-07-11).
"Mutations on the DNA-binding surface of TATA-binding protein can specifically impair the response to acidic activators in vivo" . Molecular and Cellular Biology . 15 (10): 5461–5469.
doi :
10.1128/MCB.15.10.5461 .
PMC
230796 .
PMID
7565697 .
^ Petrenko, Natalia; Yi, Jin; Dong, Liguo; Wong, Koon Ho; Struhl, Kevin (2019-01-25).
"Requirements for RNA polymerase II preinitiation complex formation in vivo" . eLife . 8 .
doi :
10.7554/eLife.43654.023 .
PMC
6366898 .
PMID
30681409 .
^ Wong, Koon Ho; Yi, Jin; Struhl, Kevin (2014-05-22).
"TFIIH phosphorylation of the Pol II CTD stimulates Mediator dissociation from the preinitiation complex and promoter escape" . Molecular Cell . 54 (4): 601–612.
doi :
10.1016/j.molcel.2014.03.024 .
PMC
4035452 .
PMID
24746699 .
^ Yi, Jin; Eser, Umut; Struhl, Kevin; Churchman, L Stirling (2017-08-24).
"The ground state and evolution of promoter regions directionality" . Cell . 170 (5): 889–898.e10.
doi :
10.1016/j.cell.2017.07.006 .
PMC
5576552 .
PMID
28803729 .
^ Struhl, Kevin (February 2007).
"Transcriptional noise and the fidelity of initiation by RNA polymerase II" . Nature Structural & Molecular Biology . 14 (2): 103–105.
doi :
10.1038/nsmb0207-103 .
PMID
17277804 .
S2CID
29398526 .
^ Moqtaderi, Zarmik; Bai, Yu; Poon, David; Weil, P Anthony; Struhl, Kevin (1996-09-12).
"TBP-associated factors are not generally required for transcriptional activation in yeast" . Nature . 383 (6596): 188–191.
doi :
10.1038/383188a0 .
PMID
8774887 .
S2CID
4351320 .
^ Kuras, Laurent; Kosa, Peter; Mencia, Mario; Struhl, Kevin (2000-05-19).
"TAF-containing and TAF-independent forms of transcriptionally active TBP in vivo" . Science . 288 (5469): 1244–1248.
doi :
10.1126/science.288.5469.1244 .
PMID
10818000 .
^ Mencia, Mario; Moqtaderi, Zarmik; Geisberg, Joseph V; Kuras, Laurent; Struhl, Kevin (April 2002).
"Activator-specific recruitment of TFIID and regulation of ribosomal protein genes in yeast" . Molecular Cell . 9 (4): 823–833.
doi :
10.1016/S1097-2765(02)00490-2 .
PMID
11983173 .
^ Fan, Xiaochun; Chou, Danny M; Struhl, Kevin (2006-01-22).
"Activator-specific recruitment of Mediator in vivo" . Nature Structural & Molecular Biology . 13 (2): 117–120.
doi :
10.1038/nsmb1049 .
PMID
16429153 .
S2CID
20626638 .
^ Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin (2016-11-03).
"Mediator Undergoes a Compositional Change during Transcriptional Activation" . Molecular Cell . 64 (3): 443–454.
doi :
10.1016/j.molcel.2016.09.015 .
PMC
5096951 .
PMID
27773675 .
^ Klein, C; Struhl, K (March 1994).
"Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity" . Molecular and Cellular Biology . 14 (3): 1920–1928.
doi :
10.1128/mcb.14.3.1920-1928.1994 .
PMC
358550 .
PMID
8114723 .
^ Wade, Joseph T; Hall, Daniel B; Struhl, Kevin (2004-12-23).
"The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes" . Nature . 432 (7020): 1054–1058.
doi :
10.1038/nature03175 .
PMID
15616568 .
S2CID
4334147 .
^ Tzamarias, D; Struhl, K (1994-06-30).
"Functional dissection of the yeast Cyc8-Tup1 transcriptional corepressor complex" . Nature . 369 (6483): 758–761.
doi :
10.1038/369758a0 .
PMID
8008070 .
S2CID
4304771 .
^ Wong, Koon Ho; Struhl, Kevin (2011-12-01).
"The Cyc8-Tup1 complex inhibits transcription primarily by masking the activation domain of the recruiting protein" . Genes & Development . 25 (23): 2525–2539.
doi :
10.1101/gad.179275.111 .
PMC
3243062 .
PMID
22156212 .
^ Proft, M; Struhl, K (June 2002).
"Hog1 kinase converts the Sko1-Cyc8-Tup1 repressor complex into an activator that recruits SAGA and SWI/SNF in response to osmotic stress" . Molecular Cell . 9 (6): 1307–1317.
doi :
10.1016/S1097-2765(02)00557-9 .
PMID
12086627 .
^ Proft, M; Struhl, K (2004-08-06).
"A MAP kinase-mediated stress relief response that precedes and regulates the timing of transcriptional induction" . Cell . 118 (3): 351–361.
doi :
10.1016/j.cell.2004.07.016 .
PMID
15294160 .
S2CID
2022911 .
^ Mason, Paul B; Struhl, Kevin (2005-03-18).
"Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo" . Molecular Cell . 17 (6): 831–840.
doi :
10.1016/j.molcel.2005.02.017 .
PMID
15780939 .
^
a
b Geisberg, Joseph V; Moqtaderi, Zarmik; Struhl, Kevin (2020-08-26).
"The transcriptional elongation rate regulates alternative polyadenylation in yeast" . eLife . 9 .
doi :
10.7554/eLife.59810.sa2 .
PMC
7532003 .
PMID
32845240 .
^ Geisberg, Joseph V; Moqtaderi, Zarmik; Fong, Nova; Erickson, Benjamin; Bentley, David L; Struhl, Kevin (2022-11-24).
"Nucleotide-level linkage of transcriptional elongation and polyadenylation" . eLife . 11 .
doi :
10.7554/eLife.83153.sa2 .
PMC
9721619 .
PMID
36421680 .
^ Geisberg, Joseph V; Moqtaderi, Zarmik; Fan, Xiaochun; Ozsolak, Fatih; Struhl, Kevin (2014-02-13).
"Global analysis of mRNA isoform half-lives reveals stabilizing and destabilizing elements in yeast" . Cell . 156 (4): 812–824.
doi :
10.1016/j.cell.2013.12.026 .
PMC
3939777 .
PMID
24529382 .
^ Moqtaderi, Zarmik; Geisberg, Joseph V; Struhl, Kevin (October 2018).
"Extensive structural differences of closely related 3' mRNA isoforms: links to Pab1 binding and mRNA stability" . Molecular Cell . 72 (5): 849–861.e6.
doi :
10.1016/j.molcel.2018.08.044 .
PMC
6289678 .
PMID
30318446 .
^ Reppas, Nikos B; Wade, Joseph T; Church, George M; Struhl, Kevin (2006-12-08).
"The transition between transcriptional initiation and elongation in E. coli is highly variable and often rate-limiting" . Molecular Cell . 24 (5): 747–757.
doi :
10.1016/j.molcel.2006.10.030 .
PMID
17157257 .
^ Wade, Joseph T; Roa, Daniel Castro; Grainger, David C; Hurd, Douglas; Busby, Stephen JW; Struhl, Kevin; Nudler, Evgeny (2006-08-06).
"Extensive functional overlap between σ factors in Escherichia coli" . Nature Structural & Molecular Biology . 13 (9): 806–814.
doi :
10.1038/nsmb1130 .
PMID
16892065 .
S2CID
19816595 .
^ Iyer, V; Struhl, K (June 1995).
"Poly(dA:dT), a ubiquitous promoter element that stimulates transcription via its intrinsic structure" . The EMBO Journal . 14 (11): 2570–2579.
doi :
10.1002/j.1460-2075.1995.tb07255.x .
PMC
398371 .
PMID
7781610 .
^ Sekinger, Edward A; Moqtaderi, Zarmik; Struhl, Kevin (2005-06-10).
"Intrinsic histone-DNA interactions and low nucleosome density are important for preferential accessibility of promoter regions in yeast" . Molecular Cell . 18 (6): 735–748.
doi :
10.1016/j.molcel.2005.05.003 .
PMID
15949447 .
^ Zhang, Yong; Moqtaderi, Zarmik; Rattner, Barbara P; Euskirchen, Ghia; Snyder, Michael; Kadonaga, James T; Liu, X Shirley; Struhl, Kevin (2009-07-20).
"Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo" . Nature Structural & Molecular Biology . 16 (8): 847–852.
doi :
10.1038/nsmb.1636 .
PMC
2823114 .
PMID
19620965 .
S2CID
11805076 .
^ Hughes, Amanda L; Jin, Yi; Rando, Oliver J; Struhl, Kevin (2012-10-12).
"A Functional Evolutionary Approach to Identify Determinants of Nucleosome Positioning: A Unifying Model for Establishing the Genome-wide Pattern" . Molecular Cell . 48 (1): 5–15.
doi :
10.1016/j.molcel.2012.07.003 .
PMC
3472102 .
PMID
22885008 .
^ Kadosh, David; Struhl, Kevin (1997-05-02).
"Repression by Ume6 Involves Recruitment of a Complex Containing Sin3 Corepressor and Rpd3 Histone Deacetylase to Target Promoters" . Cell . 89 (3): 365–371.
doi :
10.1016/S0092-8674(00)80217-2 .
PMID
9150136 .
S2CID
15115179 .
^ Kadosh, David; Struhl, Kevin (September 1998).
"Targeted Recruitment of the Sin3-Rpd3 Histone Deacetylase Complex Generates a Highly Localized Domain of Repressed Chromatin In Vivo" . Molecular and Cellular Biology . 18 (9): 5121–5127.
doi :
10.1128/MCB.18.9.5121 .
PMC
109097 .
PMID
9710596 .
^ Ng, Huck Hui; Robert, Francois; Young, Richard A; Struhl, Kevin (March 2003).
"Targeted Recruitment of Set1 Histone Methylase by Elongating Pol II Provides a Localized Mark and Memory of Recent Transcriptional Activity" . Molecular Cell . 11 (3): 709–719.
doi :
10.1016/S1097-2765(03)00092-3 .
PMID
12667453 .
^ Schwabish, Marc A; Struhl, Kevin (December 2004).
"Evidence for Eviction and Rapid Deposition of Histones upon Transcriptional Elongation by RNA Polymerase II" . Molecular and Cellular Biology . 24 (23): 10111–10117.
doi :
10.1128/MCB.24.23.10111-10117.2004 .
PMC
529037 .
PMID
15542822 .
^ Ng, Huck Hui; Feng, Qin; Wang, Hengbin; Erdjument-Bromage, Hediye; Tempst, Paul; Zhang, Yi; Struhl, Kevin (2002).
"Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association" . Genes & Development . 16 (12): 1518–1527.
doi :
10.1101/gad.1001502 .
PMC
186335 .
PMID
12080090 .
^ Ng, Huck Hui; Ciccone, David N; Morshead, Katrina B; Oettinger, Marjorie A; Struhl, Kevin (2003-02-06).
"Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: A potential mechanism for position-effect variegation" . PNAS . 100 (4): 1820–1825.
doi :
10.1073/pnas.0437846100 .
PMC
149917 .
PMID
12574507 .
^ Miotto, Benoit; Struhl, Kevin (2008).
"HBO1 histone acetylase is a coactivator of the replication licensing factor Cdt1" . Genes & Development . 22 (19): 2633–2638.
doi :
10.1101/gad.1674108 .
PMC
2559906 .
PMID
18832067 .
^ Miotto, Benoit; Struhl, Kevin (2010-01-15).
"HBO1 Histone Acetylase Activity Is Essential for DNA Replication Licensing and Inhibited by Geminin" . Molecular Cell . 37 (1): 57–66.
doi :
10.1016/j.molcel.2009.12.012 .
PMC
2818871 .
PMID
20129055 .
^ Miotto, Benoit; Struhl, Kevin (2011-10-07).
"JNK1 Phosphorylation of Cdt1 Inhibits Recruitment of HBO1 Histone Acetylase and Blocks Replication Licensing in Response to Stress" . Molecular Cell . 44 (1): 62–71.
doi :
10.1016/j.molcel.2011.06.021 .
PMC
3190045 .
PMID
21856198 .
^ Miotto, Benoit; Ji, Zhe; Struhl, Kevin (2016-06-14).
"Selectivity of ORC binding sites and the relation to replication timing, fragile sites, and deletions in cancers" . PNAS . 113 (33): 4810–4819.
doi :
10.1073/pnas.1609060113 .
PMC
4995967 .
PMID
27436900 .
^ Iliopoulos, Dimitrios; Hirsch, Heather A; Struhl, Kevin (2009-11-13).
"An Epigenetic Switch Involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation" . Cell . 139 (4): 693–706.
doi :
10.1016/j.cell.2009.10.014 .
PMC
2783826 .
PMID
19878981 .
^ He, Lizhi; Pratt, Henry; Gao, Mingshi; Wei, Fengxiang; Weng, Zhiping; Struhl, Kevin (2021-08-21).
"YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation" . eLife . 10 .
doi :
10.7554/eLife.67312 .
PMC
8463077 .
PMID
34463254 .
^ Iliopoulos, Dimitrios; Jaeger, Savina A; Hirsch, Heather A; Bulyk, Martha L; Struhl, Kevin (2010-08-27).
"STAT3 Activation of miR-21 and miR-181b-1 via PTEN and CYLD Are Part of the Epigenetic Switch Linking Inflammation to Cancer" . Molecular Cell . 39 (4): 493–506.
doi :
10.1016/j.molcel.2010.07.023 .
PMC
2929389 .
PMID
20797623 .
^ Ji, Zhe; He, Lizhi; Regev, Aviv; Struhl, Kevin (2019-03-25).
"Inflammatory regulatory network mediated by the joint action of NF-kB, STAT3, and AP-1 factors is involved in many human cancers" . PNAS . 116 (19): 9453–9462.
doi :
10.1073/pnas.1821068116 .
PMC
6511065 .
PMID
30910960 .
^ Iliopoulos, Dimitrios; Hirsch, Heather A; Wang, Guannan; Struhl, Kevin (2011-01-10).
"Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion" . PNAS . 108 (4): 1397–1402.
doi :
10.1073/pnas.1018898108 .
PMC
3029760 .
PMID
21220315 .
^ Iliopoulos, Dimitrios; Lindahl-Allen, Marianne; Polytarchou, Christos; Hirsch, Heather A; Tsichlis, Philip N; Struhl, Kevin (2010-09-10).
"Loss of miR-200 Inhibition of Suz12 Leads to Polycomb-Mediated Repression Required for the Formation and Maintenance of Cancer Stem Cells" . Molecular Cell . 39 (5): 761–772.
doi :
10.1016/j.molcel.2010.08.013 .
PMC
2938080 .
PMID
20832727 .
^ Polytarchou, Christos; Iliopoulos, Dimitrios; Struhl, Kevin (2012-08-20).
"An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state" . PNAS . 109 (36): 14470–14475.
doi :
10.1073/pnas.1212811109 .
PMC
3437881 .
PMID
22908280 .
^ Hirsch, Heather A; Iliopoulos, Dimitrios; Tsichlis, Philip N; Struhl, Kevin (2009-10-01).
"Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission" . Cancer Research . 69 (19): 7507–7511.
doi :
10.1158/0008-5472.CAN-09-2994 .
PMC
2756324 .
PMID
19752085 .
^ Iliopoulos, Dimitrios; Hirsch, Heather A; Struhl, Kevin (2011-04-29).
"Metformin Decreases the Dose of Chemotherapy for Prolonging Tumor Remission in Mouse Xenografts Involving Multiple Cancer Cell Types" . Cancer Research . 71 (9): 3196–3201.
doi :
10.1158/0008-5472.CAN-10-3471 .
PMC
3085572 .
PMID
21415163 .
^ Hirsch, Heather A; Iliopoulos, Dimitrios; Struhl, Kevin (2012-12-31).
"Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth" . PNAS . 110 (3): 972–977.
doi :
10.1073/pnas.1221055110 .
PMC
3549132 .
PMID
23277563 .
^
"American Academy of Arts & Sciences" . American Academy of Arts & Sciences . 12 July 2023.
^
"National Academy of Sciences" . National Academy of Sciences . 2014.
^
"National Academy of Medicine" . National Academy of Medicine . 2015.
^
"Who's Who Lifetime Achievement" . Who's Who Lifetime Achievement . 2018-09-13.