ASK1
ASK1
미토겐 활성 단백질 키나아제 5(MAP3K5)로도 알려진 사포시스 신호 조절 키나제 1(ASC1)은 MAP 키나제 계열이며, 미토겐 활성 단백질 키나제 경로의 일부분이다. 산화 스트레스, 소포체 내 망막 스트레스, 칼슘 유입 등 일련의 스트레스에 대응해 라프 독립 방식으로 c-Jun N-terminal kinase(JNK)와 p38 미토겐 활성 단백질 키나제를 활성화한다. ASC1은 암, 당뇨병, 류마티스 관절염, 심혈관 및 신경퇴행성 질환에 관련된 것으로 밝혀졌다.[5][6]
단백질을 위한 MAP3K5 유전자 코딩은 6번 염색체 locus 6q22.33에 위치하며, 전사 단백질은 11개의 키나제 하위 도메인을 가진 1,374개의 아미노산을 함유하고 있다.[7][citation needed] 노던 블롯 분석은 MAP3K5 대본이 인간의 심장과 췌장에 풍부하다는 것을 보여준다.[8]
활성화 메커니즘
비스트레스 조건 하에서 ASC1은 C-단자 코일 영역(CCC)을 통해 과점화되지만(활성화를 위한 요건) 티오레독신 감소(Trx)와 칼슘 및 통합결합단백질 1(CIB1)의 억제 효과에 의해 비활성 상태로 남아 있다.[9] Tx는 NCC(N-terminal coiled-coil domain)에 직접 바인딩하여 ASC1 kinase 활동을 억제한다. TRx와 CIB1은 각각 ASC1 활성화를 리독스 또는 칼슘에 민감한 방식으로 규제한다. 둘 다 ASK1 활성제인 TNF-α 수용체 관련 인자 2(TRAF2)와 경쟁하는 것으로 보인다. 그런 다음 TRAF2와 TRAF6를 ASC1에 채용하여 더 큰 분자질량 복합체를 형성한다.[10] 이후 ASC1은 CCC를 통해서뿐만 아니라 NCC를 통해서도 호모-올리고메릭적 상호작용을 형성하여, Threonine 845에서 자기인산화를 통해 ASC1의 완전한 활성화를 이끈다.[11]
ASC1 유전자 전사는 NF-kb 단백질 RelA의 활성화를 통해 IL-1, TNF-α와 같은 염증성 사이토카인에 의해 유도될 수 있다.[6] 흥미롭게도, TNF-α는 또한 디비큐튜팅을 통해 ASK1 단백질을 안정시킬 수 있다.[12] 따라서 미토겐 활성 단백질 키나아제 계열의 다른 구성원과 달리 ASK1 표현의 규제는 전사적일 뿐만 아니라 사후 전사적이다.[6]
상호작용
ASC1은 다음과 상호 작용하는 것으로 나타났다.
참조
- ^ a b c GRCh38: 앙상블 릴리스 89: ENSG00000197442 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000071369 - 앙상블, 2017년 5월
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- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^ 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. 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.
외부 링크
- UCSC 게놈 브라우저의 인간 MAP3K5 게놈 위치 및 MAP3K5 유전자 세부 정보 페이지.
- PDB의 UniProt: Q99683(Mitgen-activated 단백질 키나제 키나제 키나제 5)에 대한 PDB의 모든 구조 정보 개요.
추가 읽기
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- 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.
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- 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.
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- 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.
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