ASK1
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| Location (UCSC) | Chr 6: 136.56 – 136.79 Mb | Chr 10: 19.81 – 20.02 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase kinase 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
Interactions
ASK1 has been shown to
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.
- PMID 19389260.
- ^ S2CID 4863537.
- PMID 9465908.
- ^ "Entrez Gene: MAP3K5 mitogen-activated protein kinase kinase kinase 5".
- PMID 19805025.
- PMID 16129676.
- PMID 17724081.
- PMID 16407264.
- PMID 11427728.
- PMID 11416155.
- PMID 9743501.
- PMID 11959862.
- PMID 12473108.
- S2CID 5250125.
- PMID 12391142.
- ^ PMID 11689443.
- PMID 12820963.
- ^ PMID 10921914.
- PMID 12189133.
- S2CID 9264865.
- ^ PMID 17015619.
- ^ PMID 9774977.
- ^ S2CID 12132452.
External links
- Human MAP3K5 genome location and MAP3K5 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: Q99683 (Mitogen-activated protein kinase kinase kinase 5) at the PDBe-KB.
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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. S2CID 4414424.
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