From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
Apoptosis signal-regulating kinase 1 (ASK1 ) also known as mitogen-activated protein kinase 5 (MAP3K5 ) is a member of MAP kinase family and as such a part of
mitogen-activated protein kinase pathway. It activates
c-Jun N-terminal kinase (JNK) and
p38 mitogen-activated protein kinases in a Raf-independent fashion in response to an array of stresses such as
oxidative stress ,
endoplasmic reticulum stress and calcium influx. ASK1 has been found to be involved in cancer, diabetes,
rheumatoid arthritis , cardiovascular and neurodegenerative diseases.
[5]
[6]
MAP3K5 gene coding for the protein is located on chromosome 6 at
locus 6q22.33.
[7] and the transcribed protein contains 1,374 amino acids with 11 kinase subdomains.[
citation needed ] Northern blot analysis shows that MAP3K5 transcript is abundant in human heart and pancreas.
[8]
Mechanism of activation
Under nonstress conditions ASK1 is oligomerized (a requirement for its activation) through its C-terminal
coiled-coil domain (CCC), but remains in an inactive form by the suppressive effect of reduced thioredoxin (
Trx ) and calcium and integrin binding protein 1 (
CIB1 ).
[9] Trx inhibits ASK1 kinase activity by direct binding to its N-terminal coiled-coil domain (NCC). Trx and CIB1 regulate ASK1 activation in a redox- or calcium- sensitive manner, respectively. Both appear to compete with TNF-α receptor-associated factor 2 (TRAF2), an ASK1 activator.
TRAF2 and
TRAF6 are then recruited to ASK1 to form a larger molecular mass complex.
[10] Subsequently, ASK1 forms homo-oligomeric interactions not only through the CCC, but also the NCC, which leads to full activation of ASK1 through autophosphorylation at threonine 845.
[11]
ASK1 gene transcription can be induced by inflammatory cytokines such as IL-1 and TNF-α through the activation of the
NF-kb protein RelA.
[6] Interestingly,
TNF-α is also able to stabilize the ASK1 protein through
deubiquitination .
[12] Thus, unlike other members of the mitogen-activated protein kinase family, the regulation of ASK1 expression is transcriptional as well as
post-transcriptional .
[6]
Interactions
ASK1 has been shown to
interact with:
C-Raf ,
[13]
CDC25A ,
[14]
DAXX ,
[15]
DUSP19 ,
[16]
EIF2AK2 ,
[17]
GADD45B ,
[18]
HSPA1A ,
[19]
MAP2K6 ,
[20]
[21]
MAP3K7
[22] and
MAPK8IP3 ,
[23]
PDCD6 ,
[24]
PPP5C ,
[20]
RB1CC1 ,
[25]
TRAF2 ,
[25]
[26]
TRAF5 ,
[26]
[27] and
TRAF6 .
[22]
[26]
[27]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000197442 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000071369 –
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 .
^ Hattori K, Naguro I, Runchel C, Ichijo H (April 2009).
"The roles of ASK family proteins in stress responses and diseases" . Cell Communication and Signaling . 7 : 9.
doi :
10.1186/1478-811X-7-9 .
PMC
2685135 .
PMID
19389260 .
^
a
b
c Nygaard G, Di Paolo JA, Hammaker D, Boyle DL, Budas G, Notte GT, et al. (May 2018). "Regulation and function of apoptosis signal-regulating kinase 1 in rheumatoid arthritis". Biochemical Pharmacology . 151 : 282–290.
doi :
10.1016/j.bcp.2018.01.041 .
PMID
29408488 .
S2CID
4863537 .
^ Rampoldi L, Zimbello R, Bortoluzzi S, Tiso N, Valle G, Lanfranchi G, Danieli GA (1997). "Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5". Cytogenetics and Cell Genetics . 78 (3–4): 301–3.
doi :
10.1159/000134677 .
PMID
9465908 .
^
"Entrez Gene: MAP3K5 mitogen-activated protein kinase kinase kinase 5" .
^ Yoon KW, Cho JH, Lee JK, Kang YH, Chae JS, Kim YM, et al. (October 2009).
"CIB1 functions as a Ca(2+)-sensitive modulator of stress-induced signaling by targeting ASK1" . Proceedings of the National Academy of Sciences of the United States of America . 106 (41): 17389–94.
Bibcode :
2009PNAS..10617389Y .
doi :
10.1073/pnas.0812259106 .
PMC
2762684 .
PMID
19805025 .
^ Noguchi T, Takeda K, Matsuzawa A, Saegusa K, Nakano H, Gohda J, et al. (November 2005).
"Recruitment of tumor necrosis factor receptor-associated factor family proteins to apoptosis signal-regulating kinase 1 signalosome is essential for oxidative stress-induced cell death" . The Journal of Biological Chemistry . 280 (44): 37033–40.
doi :
10.1074/jbc.M506771200 .
PMID
16129676 .
^ Fujino G, Noguchi T, Matsuzawa A, Yamauchi S, Saitoh M, Takeda K, Ichijo H (December 2007).
"Thioredoxin and TRAF family proteins regulate reactive oxygen species-dependent activation of ASK1 through reciprocal modulation of the N-terminal homophilic interaction of ASK1" . Molecular and Cellular Biology . 27 (23): 8152–63.
doi :
10.1128/MCB.00227-07 .
PMC
2169188 .
PMID
17724081 .
^ He Y, Zhang W, Zhang R, Zhang H, Min W (March 2006).
"SOCS1 inhibits tumor necrosis factor-induced activation of ASK1-JNK inflammatory signaling by mediating ASK1 degradation" . The Journal of Biological Chemistry . 281 (9): 5559–66.
doi :
10.1074/jbc.M512338200 .
PMID
16407264 .
^ Chen J, Fujii K, Zhang L, Roberts T, Fu H (July 2001).
"Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism" . Proceedings of the National Academy of Sciences of the United States of America . 98 (14): 7783–8.
Bibcode :
2001PNAS...98.7783C .
doi :
10.1073/pnas.141224398 .
PMC
35419 .
PMID
11427728 .
^ Zou X, Tsutsui T, Ray D, Blomquist JF, Ichijo H, Ucker DS, Kiyokawa H (July 2001).
"The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis signal-regulating kinase 1" . Molecular and Cellular Biology . 21 (14): 4818–28.
doi :
10.1128/MCB.21.14.4818-4828.2001 .
PMC
87174 .
PMID
11416155 .
^
Chang HY , Nishitoh H, Yang X, Ichijo H, Baltimore D (September 1998). "Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx". Science . 281 (5384): 1860–3.
Bibcode :
1998Sci...281.1860C .
doi :
10.1126/science.281.5384.1860 .
PMID
9743501 .
^ Zama T, Aoki R, Kamimoto T, Inoue K, Ikeda Y, Hagiwara M (June 2002).
"Scaffold role of a mitogen-activated protein kinase phosphatase, SKRP1, for the JNK signaling pathway" . The Journal of Biological Chemistry . 277 (26): 23919–26.
doi :
10.1074/jbc.M200838200 .
PMID
11959862 .
^ Takizawa T, Tatematsu C, Nakanishi Y (December 2002).
"Double-stranded RNA-activated protein kinase interacts with apoptosis signal-regulating kinase 1. Implications for apoptosis signaling pathways" . European Journal of Biochemistry . 269 (24): 6126–32.
doi :
10.1046/j.1432-1033.2002.03325.x .
PMID
12473108 .
^ Papa S, Zazzeroni F, Bubici C, Jayawardena S, Alvarez K, Matsuda S, et al. (February 2004). "Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2". Nature Cell Biology . 6 (2): 146–53.
doi :
10.1038/ncb1093 .
PMID
14743220 .
S2CID
5250125 .
^ Park HS, Cho SG, Kim CK, Hwang HS, Noh KT, Kim MS, et al. (November 2002).
"Heat shock protein hsp72 is a negative regulator of apoptosis signal-regulating kinase 1" . Molecular and Cellular Biology . 22 (22): 7721–30.
doi :
10.1128/MCB.22.22.7721-7730.2002 .
PMC
134722 .
PMID
12391142 .
^
a
b Morita K, Saitoh M, Tobiume K, Matsuura H, Enomoto S, Nishitoh H, Ichijo H (November 2001).
"Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress" . The EMBO Journal . 20 (21): 6028–36.
doi :
10.1093/emboj/20.21.6028 .
PMC
125685 .
PMID
11689443 .
^ Huang S, Shu L, Dilling MB, Easton J, Harwood FC, Ichijo H, Houghton PJ (June 2003).
"Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1)" . Molecular Cell . 11 (6): 1491–501.
doi :
10.1016/S1097-2765(03)00180-1 .
PMID
12820963 .
^
a
b Mochida Y, Takeda K, Saitoh M, Nishitoh H, Amagasa T, Ninomiya-Tsuji J, et al. (October 2000).
"ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction" . The Journal of Biological Chemistry . 275 (42): 32747–52.
doi :
10.1074/jbc.M003042200 .
PMID
10921914 .
^ Matsuura H, Nishitoh H, Takeda K, Matsuzawa A, Amagasa T, Ito M, et al. (October 2002).
"Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade" . The Journal of Biological Chemistry . 277 (43): 40703–9.
doi :
10.1074/jbc.M202004200 .
hdl :
2297/2692 .
PMID
12189133 .
^ Hwang IS, Jung YS, Kim E (October 2002). "Interaction of ALG-2 with ASK1 influences ASK1 localization and subsequent JNK activation". FEBS Letters . 529 (2–3): 183–7.
doi :
10.1016/S0014-5793(02)03329-X .
PMID
12372597 .
S2CID
9264865 .
^
a
b Gan B, Peng X, Nagy T, Alcaraz A, Gu H, Guan JL (October 2006).
"Role of FIP200 in cardiac and liver development and its regulation of TNFalpha and TSC-mTOR signaling pathways" . The Journal of Cell Biology . 175 (1): 121–33.
doi :
10.1083/jcb.200604129 .
PMC
2064504 .
PMID
17015619 .
^
a
b
c Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, et al. (September 1998).
"ASK1 is essential for JNK/SAPK activation by TRAF2" . Molecular Cell . 2 (3): 389–95.
doi :
10.1016/S1097-2765(00)80283-X .
PMID
9774977 .
^
a
b Hoeflich KP, Yeh WC, Yao Z, Mak TW, Woodgett JR (October 1999). "Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1)". Oncogene . 18 (42): 5814–20.
doi :
10.1038/sj.onc.1202975 .
PMID
10523862 .
S2CID
12132452 .
External links
Further reading
Hayakawa T, Matsuzawa A, Noguchi T, Takeda K, Ichijo H (April 2006).
"The ASK1-MAP kinase pathways in immune and stress responses" . Microbes and Infection . 8 (4): 1098–107.
doi :
10.1016/j.micinf.2005.12.001 .
PMID
16517200 .
Nagai H, Noguchi T, Takeda K, Ichijo H (January 2007).
"Pathophysiological roles of ASK1-MAP kinase signaling pathways" . Journal of Biochemistry and Molecular Biology . 40 (1): 1–6.
doi :
10.5483/BMBRep.2007.40.1.001 .
PMID
17244475 .
Wang XS, Diener K, Jannuzzi D, Trollinger D, Tan TH, Lichenstein H, et al. (December 1996).
"Molecular cloning and characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase" . The Journal of Biological Chemistry . 271 (49): 31607–11.
doi :
10.1074/jbc.271.49.31607 .
PMID
8940179 .
Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, et al. (January 1997). "Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways". Science . 275 (5296): 90–4.
doi :
10.1126/science.275.5296.90 .
PMID
8974401 .
S2CID
23981616 .
Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, et al. (May 1998).
"Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1" . The EMBO Journal . 17 (9): 2596–606.
doi :
10.1093/emboj/17.9.2596 .
PMC
1170601 .
PMID
9564042 .
Chang HY, Nishitoh H, Yang X, Ichijo H, Baltimore D (September 1998). "Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx". Science . 281 (5384): 1860–3.
Bibcode :
1998Sci...281.1860C .
doi :
10.1126/science.281.5384.1860 .
PMID
9743501 .
Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, et al. (September 1998).
"ASK1 is essential for JNK/SAPK activation by TRAF2" . Molecular Cell . 2 (3): 389–95.
doi :
10.1016/S1097-2765(00)80283-X .
PMID
9774977 .
Wang XS, Diener K, Tan TH, Yao Z (December 1998). "MAPKKK6, a novel mitogen-activated protein kinase kinase kinase, that associates with MAPKKK5". Biochemical and Biophysical Research Communications . 253 (1): 33–7.
doi :
10.1006/bbrc.1998.9749 .
PMID
9875215 .
Zhang L, Chen J, Fu H (July 1999).
"Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins" . Proceedings of the National Academy of Sciences of the United States of America . 96 (15): 8511–5.
Bibcode :
1999PNAS...96.8511Z .
doi :
10.1073/pnas.96.15.8511 .
PMC
17547 .
PMID
10411906 .
Hoeflich KP, Yeh WC, Yao Z, Mak TW, Woodgett JR (October 1999). "Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1)". Oncogene . 18 (42): 5814–20.
doi :
10.1038/sj.onc.1202975 .
PMID
10523862 .
S2CID
12132452 .
Takeda K, Hatai T, Hamazaki TS, Nishitoh H, Saitoh M, Ichijo H (March 2000).
"Apoptosis signal-regulating kinase 1 (ASK1) induces neuronal differentiation and survival of PC12 cells" . The Journal of Biological Chemistry . 275 (13): 9805–13.
doi :
10.1074/jbc.275.13.9805 .
PMID
10734135 .
Charette SJ, Lavoie JN, Lambert H, Landry J (October 2000).
"Inhibition of Daxx-mediated apoptosis by heat shock protein 27" . Molecular and Cellular Biology . 20 (20): 7602–12.
doi :
10.1128/MCB.20.20.7602-7612.2000 .
PMC
86317 .
PMID
11003656 .
Ko YG, Kim EY, Kim T, Park H, Park HS, Choi EJ, Kim S (February 2001).
"Glutamine-dependent antiapoptotic interaction of human glutaminyl-tRNA synthetase with apoptosis signal-regulating kinase 1" . The Journal of Biological Chemistry . 276 (8): 6030–6.
doi :
10.1074/jbc.M006189200 .
PMID
11096076 .
Kim AH, Khursigara G, Sun X, Franke TF, Chao MV (February 2001).
"Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1" . Molecular and Cellular Biology . 21 (3): 893–901.
doi :
10.1128/MCB.21.3.893-901.2001 .
PMC
86680 .
PMID
11154276 .
Cho SG, Lee YH, Park HS, Ryoo K, Kang KW, Park J, et al. (April 2001).
"Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1" . The Journal of Biological Chemistry . 276 (16): 12749–55.
doi :
10.1074/jbc.M005561200 .
PMID
11278289 .
Geleziunas R, Xu W, Takeda K, Ichijo H, Greene WC (April 2001). "HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell". Nature . 410 (6830): 834–8.
Bibcode :
2001Natur.410..834G .
doi :
10.1038/35071111 .
PMID
11298454 .
S2CID
4414424 .
Activity Regulation Classification Kinetics Types