피카드
PYCARD
흔히 ASC(Apoptosis와 연관된 CARD를 함유한 점성 단백질)로 불리는 PYCARD는 인간에서 PYCARD 유전자에 의해 인코딩되는 단백질이다.[5]주로 단세포와 대식세포의 핵에 국부화되어 있다.다만 병원체 감염의 경우 세포질, 과핵 공간, 소포체 망막, 미토콘드리아 등으로 빠르게 다시 칼로리를 높이며, 인플람마솜 활성화의 핵심 적응단백질이다.[6]
전체 길이 ASC의 NMR 구조: PDB ID 2KN6 [7][1]
함수
이 유전자는 N-단백질 PYRIN-PAAD-DAPIN 도메인(PYD)과 C-단백질 캐스파제-채용 도메인(CARD)의 두 개의 단백질-단백질 상호작용 영역으로 구성된 어댑터 단백질을 인코딩한다.PYD와 CARD 도메인은 캐스파제의 활성화를 통해 염증성 및 사포성 신호 경로에서 대형 신호 복합체의 조립을 매개하는 6헥스 다발 데스 도메인-폴드 슈퍼 패밀리의 구성원이다.정상 세포에서는 이 단백질이 세포질에 국부화되어 있지만, 세포사멸을 겪고 있는 세포에서는 핵 주변부 근처에 공과 같은 골재를 형성한다.
PYCARD는 네 가지 다른 ISO 형태로 발생할 수 있다.흔히 표준 PYCARD라고 불리는 ISOform 1과 ISOform 2는 활성형 이소폼이다.그들은 뉴클레오티드 과점 도메인 유사 수용체(NLR)와 캐스파제-1과 공동 국산화한다.이소폼 1과는 달리, 이소폼 2는 직접 IL-1β 처리 규제에 관여한다.Isoform 3은 억제형 이소형으로, Caspase-1과 함께 국산화만 할 뿐 NLR과는 공동 국산화하지 않는다.Isoform 4는 NLR 신호 전달에서 어댑터 단백질 역할을 할 수 없으며 그 역할은 여전히 이해하기 어렵다.[6]
상호작용
PYCARD는 MEFV와 상호작용하는 것으로 나타났다.[8]
참조
- ^ a b c GRCh38: 앙상블 릴리스 89: ENSG00000103490 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000030793 - 앙상블, 2017년 5월
- ^ "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.
- ^ "Entrez Gene: PYCARD PYD and CARD domain containing". Retrieved 18 September 2010.
- ^ a b Dunn, JH; Fujita, M (2015). "PYCARD (PYD and CARD domain containing)". Atlas of Genetics and Cytogenetics in Oncology and Haematology (4). doi:10.4267/2042/56440. hdl:2042/56440. ISSN 1768-3262.
- ^ Alba, Eva de (2009-11-20). "Structure and Interdomain Dynamics of Apoptosis-associated Speck-like Protein Containing a CARD (ASC)". Journal of Biological Chemistry. 284 (47): 32932–32941. doi:10.1074/jbc.M109.024273. ISSN 0021-9258. PMC 2781708. PMID 19759015.
- ^ Richards N, Schaner P, Diaz A, Stuckey J, Shelden E, Wadhwa A, Gumucio DL (October 2001). "Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis". J. Biol. Chem. 276 (42): 39320–9. doi:10.1074/jbc.M104730200. PMID 11498534.
추가 읽기
- Masumoto J, Taniguchi S, Ayukawa K, Sarvotham H, Kishino T, Niikawa N, Hidaka E, Katsuyama T, Higuchi T, Sagara J (1999). "ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells". J. Biol. Chem. 274 (48): 33835–8. doi:10.1074/jbc.274.48.33835. PMID 10567338.
- Lee SK, Na SY, Jung SY, Choi JE, Jhun BH, Cheong J, Meltzer PS, Lee YC, Lee JW (2000). "Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2". Mol. Endocrinol. 14 (6): 915–25. doi:10.1210/mend.14.6.0471. PMID 10847592.
- Conway KE, McConnell BB, Bowring CE, Donald CD, Warren ST, Vertino PM (2000). "TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers". Cancer Res. 60 (22): 6236–42. PMID 11103776.
- McConnell BB, Vertino PM (2000). "Activation of a caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain protein TMS1". Cancer Res. 60 (22): 6243–7. PMID 11103777.
- Martinon F, Hofmann K, Tschopp J (2001). "The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation". Curr. Biol. 11 (4): R118-20. doi:10.1016/S0960-9822(01)00056-2. PMID 11250163. S2CID 18564343.
- Geddes BJ, Wang L, Huang WJ, Lavellee M, Manji GA, Brown M, Jurman M, Cao J, Morgenstern J, Merriam S, Glucksmann MA, DiStefano PS, Bertin J (2001). "Human CARD12 is a novel CED4/Apaf-1 family member that induces apoptosis". Biochem. Biophys. Res. Commun. 284 (1): 77–82. doi:10.1006/bbrc.2001.4928. PMID 11374873.
- Richards N, Schaner P, Diaz A, Stuckey J, Shelden E, Wadhwa A, Gumucio DL (2001). "Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis". J. Biol. Chem. 276 (42): 39320–9. doi:10.1074/jbc.M104730200. PMID 11498534.
- Stimson KM, Vertino PM (2002). "Methylation-mediated silencing of TMS1/ASC is accompanied by histone hypoacetylation and CpG island-localized changes in chromatin architecture". J. Biol. Chem. 277 (7): 4951–8. doi:10.1074/jbc.M109809200. PMID 11733524.
- Manji GA, Wang L, Geddes BJ, Brown M, Merriam S, Al-Garawi A, Mak S, Lora JM, Briskin M, Jurman M, Cao J, DiStefano PS, Bertin J (2002). "PYPAF1, a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B". J. Biol. Chem. 277 (13): 11570–5. doi:10.1074/jbc.M112208200. PMID 11786556.
- Srinivasula SM, Poyet JL, Razmara M, Datta P, Zhang Z, Alnemri ES (2002). "The PYRIN-CARD protein ASC is an activating adaptor for caspase-1". J. Biol. Chem. 277 (24): 21119–22. doi:10.1074/jbc.C200179200. PMID 11967258.
- Wang L, Manji GA, Grenier JM, Al-Garawi A, Merriam S, Lora JM, Geddes BJ, Briskin M, DiStefano PS, Bertin J (2002). "PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing". J. Biol. Chem. 277 (33): 29874–80. doi:10.1074/jbc.M203915200. PMID 12019269.
- Shiohara M, Taniguchi S, Masumoto J, Yasui K, Koike K, Komiyama A, Sagara J (2002). "ASC, which is composed of a PYD and a CARD, is up-regulated by inflammation and apoptosis in human neutrophils". Biochem. Biophys. Res. Commun. 293 (5): 1314–8. doi:10.1016/S0006-291X(02)00384-4. PMID 12054656.
- Martinon F, Burns K, Tschopp J (2002). "The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta". Mol. Cell. 10 (2): 417–26. doi:10.1016/S1097-2765(02)00599-3. PMID 12191486.
- Stehlik C, Fiorentino L, Dorfleutner A, Bruey JM, Ariza EM, Sagara J, Reed JC (2002). "The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step in nuclear factor kappaB activation pathways". J. Exp. Med. 196 (12): 1605–15. doi:10.1084/jem.20021552. PMC 2196065. PMID 12486103.
- Moriai R, Tsuji N, Kobayashi D, Yagihashi A, Namiki Y, Takahashi H, Watanabe N (2003). "A proapoptotic caspase recruitment domain protein gene, TMS1, is hypermethylated in human breast and gastric cancers". Anticancer Res. 22 (6C): 4163–8. PMID 12553049.
- Dowds TA, Masumoto J, Chen FF, Ogura Y, Inohara N, Núñez G (2003). "Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene product". Biochem. Biophys. Res. Commun. 302 (3): 575–80. doi:10.1016/S0006-291X(03)00221-3. PMID 12615073.
- Masumoto J, Dowds TA, Schaner P, Chen FF, Ogura Y, Li M, Zhu L, Katsuyama T, Sagara J, Taniguchi S, Gumucio DL, Núñez G, Inohara N (2003). "ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis". Biochem. Biophys. Res. Commun. 303 (1): 69–73. doi:10.1016/S0006-291X(03)00309-7. PMID 12646168.
- Stehlik C, Krajewska M, Welsh K, Krajewski S, Godzik A, Reed JC (2003). "The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-mediated nuclear-factor-kappa B and pro-caspase-1 regulation". Biochem. J. 373 (Pt 1): 101–13. doi:10.1042/BJ20030304. PMC 1223462. PMID 12656673.
- Levine JJ, Stimson-Crider KM, Vertino PM (2003). "Effects of methylation on expression of TMS1/ASC in human breast cancer cells". Oncogene. 22 (22): 3475–88. doi:10.1038/sj.onc.1206430. PMID 12776200.
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