From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
MKL/megakaryoblastic leukemia 1 (also termed MRTFA/myocardin related transcription factor A) is a
protein that in humans is encoded by the MKL1
gene .
[5]
[6]
[7]
[8]
Function
The protein encoded by this gene is regulated by the actin cytoskeleton and is shuttled between the cytoplasm and the nucleus as a result of actin dynamics.
[9] In the nucleus, it coactivates the transcription factor
serum response factor ,
[10] a key regulator of smooth muscle cell differentiation, in an interaction mediated by its Basic domain. It is closely related to
MKL2 and
myocardin , with which it shares five key conserved structural domains.
[11]
Clinical significance
This gene is involved in a specific translocation event that creates a fusion of this gene and the RNA-binding motif protein-15 gene. This translocation has been associated with
acute megakaryocytic leukemia .
[8] It also functions in the process of normal megakaryocyte maturation.
[12]
Research
Evalarted MKL1 expression is observed in breast cancer and can predict chemosensitivity and patient survival. MKL1 may be a promising biomarker of clinical value for breast cancer.
[13]
See also
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000196588 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000042292 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Ma Z, Morris SW, Valentine V, Li M, Herbrick JA, Cui X, et al. (July 2001). "Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia". Nature Genetics . 28 (3): 220–221.
doi :
10.1038/90054 .
PMID
11431691 .
S2CID
36236342 .
^ Sasazuki T, Sawada T, Sakon S, Kitamura T, Kishi T, Okazaki T, et al. (August 2002).
"Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death" . The Journal of Biological Chemistry . 277 (32): 28853–28860.
doi :
10.1074/jbc.M203190200 .
PMID
12019265 .
^ Du KL, Chen M, Li J, Lepore JJ, Mericko P, Parmacek MS (April 2004).
"Megakaryoblastic leukemia factor-1 transduces cytoskeletal signals and induces smooth muscle cell differentiation from undifferentiated embryonic stem cells" . The Journal of Biological Chemistry . 279 (17): 17578–17586.
doi :
10.1074/jbc.M400961200 .
PMID
14970199 .
^
a
b
"Entrez Gene: MKL1 megakaryoblastic leukemia (translocation) 1" .
^ Vartiainen MK, Guettler S, Larijani B, Treisman R (June 2007). "Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL". Science . 316 (5832): 1749–1752.
Bibcode :
2007Sci...316.1749V .
doi :
10.1126/science.1141084 .
PMID
17588931 .
S2CID
44910416 .
^ Miralles F, Posern G, Zaromytidou AI, Treisman R (May 2003).
"Actin dynamics control SRF activity by regulation of its coactivator MAL" . Cell . 113 (3): 329–342.
doi :
10.1016/S0092-8674(03)00278-2 .
PMID
12732141 .
^ Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, et al. (November 2002).
"Potentiation of serum response factor activity by a family of myocardin-related transcription factors" . Proceedings of the National Academy of Sciences of the United States of America . 99 (23): 14855–14860.
Bibcode :
2002PNAS...9914855W .
doi :
10.1073/pnas.222561499 .
PMC
137508 .
PMID
12397177 .
^ Cheng EC, Luo Q, Bruscia EM, Renda MJ, Troy JA, Massaro SA, et al. (March 2009).
"Role for MKL1 in megakaryocytic maturation" . Blood . 113 (12): 2826–2834.
doi :
10.1182/blood-2008-09-180596 .
PMC
2661865 .
PMID
19136660 .
^ Hua Y, Yang M (June 2022).
"The prognostic value of MKL1 in predicting breast cancer immune infiltrates and chemosensitivity" . Bosnian Journal of Basic Medical Sciences . 22 (3): 382–394.
doi :
10.17305/bjbms.2021.6306 .
PMC
9162751 .
PMID
34761735 .
Further reading
Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (June 2002).
"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones" . DNA Research . 9 (3): 99–106.
doi :
10.1093/dnares/9.3.99 .
PMID
12168954 .
Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, et al. (December 1999).
"The DNA sequence of human chromosome 22" . Nature . 402 (6761): 489–495.
Bibcode :
1999Natur.402..489D .
doi :
10.1038/990031 .
PMID
10591208 .
Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (February 2000).
"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro" . DNA Research . 7 (1): 65–73.
doi :
10.1093/dnares/7.1.65 .
PMID
10718198 .
Mercher T, Coniat MB, Monni R, Mauchauffe M, Nguyen Khac F, Gressin L, et al. (May 2001).
"Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia" . Proceedings of the National Academy of Sciences of the United States of America . 98 (10): 5776–5779.
Bibcode :
2001PNAS...98.5776M .
doi :
10.1073/pnas.101001498 .
PMC
33289 .
PMID
11344311 .
Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, et al. (June 2001).
"Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor" . Cell . 105 (7): 851–862.
doi :
10.1016/S0092-8674(01)00404-4 .
PMID
11439182 .
Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, et al. (November 2002).
"Potentiation of serum response factor activity by a family of myocardin-related transcription factors" . Proceedings of the National Academy of Sciences of the United States of America . 99 (23): 14855–14860.
Bibcode :
2002PNAS...9914855W .
doi :
10.1073/pnas.222561499 .
PMC
137508 .
PMID
12397177 .
Cen B, Selvaraj A, Burgess RC, Hitzler JK, Ma Z, Morris SW, Prywes R (September 2003).
"Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes" . Molecular and Cellular Biology . 23 (18): 6597–6608.
doi :
10.1128/MCB.23.18.6597-6608.2003 .
PMC
193697 .
PMID
12944485 .
Selvaraj A, Prywes R (October 2003).
"Megakaryoblastic leukemia-1/2, a transcriptional co-activator of serum response factor, is required for skeletal myogenic differentiation" . The Journal of Biological Chemistry . 278 (43): 41977–41987.
doi :
10.1074/jbc.M305679200 .
PMID
14565952 .
Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (August 2004).
"Large-scale characterization of HeLa cell nuclear phosphoproteins" . Proceedings of the National Academy of Sciences of the United States of America . 101 (33): 12130–12135.
Bibcode :
2004PNAS..10112130B .
doi :
10.1073/pnas.0404720101 .
PMC
514446 .
PMID
15302935 .
Selvaraj A, Prywes R (August 2004).
"Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent" . BMC Molecular Biology . 5 : 13.
doi :
10.1186/1471-2199-5-13 .
PMC
516031 .
PMID
15329155 .
Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, et al. (2005).
"A genome annotation-driven approach to cloning the human ORFeome" . Genome Biology . 5 (10): R84.
doi :
10.1186/gb-2004-5-10-r84 .
PMC
545604 .
PMID
15461802 .
Hsiao HH, Yang MY, Liu YC, Hsiao HP, Tseng SB, Chao MC, et al. (May 2005).
"RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient" . American Journal of Hematology . 79 (1): 43–45.
doi :
10.1002/ajh.20298 .
PMID
15849773 .
S2CID
30859557 .
Nakagawa K, Kuzumaki N (August 2005).
"Transcriptional activity of megakaryoblastic leukemia 1 (MKL1) is repressed by SUMO modification" . Genes to Cells . 10 (8): 835–850.
doi :
10.1111/j.1365-2443.2005.00880.x .
PMID
16098147 .