TSC1

TSC1
TSC1
사용 가능한 구조물
PDB직교 검색: PDBe RCSB
식별자
별칭TSC1, LAM, TSC, 결핵성 경화증 1, TSC 복합 소단위 1
외부 IDOMIM: 605284 MGI: 1929183 HomoloGene: 314 GeneCard: TSC1
직교체
종인간마우스
엔트레스

7248

64930

앙상블

ENSG00000165699

ENSMUSG00000026812

유니프로트

Q92574

Q9EP53

RefSeq(mRNA)

NM_000368
NM_001008567
NM_001162426
NM_001162427
NM_001362177

NM_022887
NM_001289575
NM_001289576

RefSeq(단백질)

NP_000359
NP_001155898
NP_001155899
NP_001349106

NP_001276504
NP_001276505
NP_075025

위치(UCSC)Cr 9: 132.89 – 132.95MbChr 2: 28.64 – 28.69Mb
PubMed 검색[3][4]
위키다타
인간 보기/편집마우스 보기/편집

하마르틴으로도 알려진 결핵성 경화증 1(TSC1)은 인간에서 TSC1 유전자에 의해 인코딩되는 단백질이다.[5]

함수

TSC1은 Caperone Hsp90(열충격 단백질-90)의 ATPase 활동을 억제하고 Caperone 사이클을 감속하는 공동 Caperone의 기능을 한다. Tsc1은 Tsc2를 포함한 키나제 및 비키나제 클라이언트를 보호함에 있어 Hsp90의 촉진자 역할을 하므로 프로테아솜에서 이들의 편재 및 저하를 방지한다.[6] TSC1, TSC2, TBC1D7은 TSC 복합체라고도 알려진 다단백질 복합체다. 이 단지는 mTORC1의 필수 활성제인 소형 GTPase Rheb의 GTPase-활성화 단백질(GAP)으로 기능함으로써 mTORC1 신호를 부정적으로 조절한다. TSC 복합체가 종양 억제기로 연루되었다.

임상적 유의성

이 유전자의 결함은 TSC 복합체의 기능 손상으로 인해 결핵 경화증을 일으킬 수 있다.[citation needed] TSC1의 결함은 초점 피질 이형화의 원인이 될 수도 있다.[citation needed] TSC1은 해마의 CA3 영역에 있는 뇌 신경 세포들을 뇌졸중의 영향으로부터 보호하는 데 관여할 수 있다.[7]

상호작용

TSC1은 다음과 상호 작용하는 것으로 나타났다.

참고 항목

참조

  1. ^ a b c GRCh38: 앙상블 릴리스 89: ENSG00000165699 - 앙상블, 2017년 5월
  2. ^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000026812 - 앙상블, 2017년 5월
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: TSC1 tuberous sclerosis 1".
  6. ^ a b c Woodford MR, Sager RA, Marris E, Dunn DM, Blanden AR, Murphy RL, Rensing N, Shapiro O, Panaretou B, Prodromou C, Loh SN, Gutmann DH, Bourboulia D, Bratslavsky G, Wong M, Mollapour M (December 2017). "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients". The EMBO Journal. 36 (24): 3650–3665. doi:10.15252/embj.201796700. PMC 5730846. PMID 29127155.
  7. ^ Papadakis M, Hadley G, Xilouri M, Hoyte LC, Nagel S, McMenamin MM, Tsaknakis G, Watt SM, Drakesmith CW, Chen R, Wood MJ, Zhao Z, Kessler B, Vekrellis K, Buchan AM (March 2013). "Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy". Nature Medicine. 19 (3): 351–7. doi:10.1038/nm.3097. PMC 3744134. PMID 23435171.
  8. ^ Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J (September 2004). "Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase". Proceedings of the National Academy of Sciences of the United States of America. 101 (37): 13489–94. Bibcode:2004PNAS..10113489R. doi:10.1073/pnas.0405659101. PMC 518784. PMID 15342917.
  9. ^ a b Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ, Cheng JQ (September 2002). "Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin". The Journal of Biological Chemistry. 277 (38): 35364–70. doi:10.1074/jbc.M205838200. PMID 12167664.
  10. ^ Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, Ramesh V (November 2002). "The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton". The Journal of Biological Chemistry. 277 (46): 44180–6. doi:10.1074/jbc.M207211200. PMID 12226091.
  11. ^ a b Astrinidis A, Senapedis W, Henske EP (January 2006). "Hamartin, the tuberous sclerosis complex 1 gene product, interacts with polo-like kinase 1 in a phosphorylation-dependent manner". Human Molecular Genetics. 15 (2): 287–97. doi:10.1093/hmg/ddi444. PMID 16339216.
  12. ^ Hodges AK, Li S, Maynard J, Parry L, Braverman R, Cheadle JP, DeClue JE, Sampson JR (December 2001). "Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin". Human Molecular Genetics. 10 (25): 2899–905. doi:10.1093/hmg/10.25.2899. PMID 11741833.
  13. ^ Aicher LD, Campbell JS, Yeung RS (June 2001). "Tuberin phosphorylation regulates its interaction with hamartin. Two proteins involved in tuberous sclerosis". The Journal of Biological Chemistry. 276 (24): 21017–21. doi:10.1074/jbc.C100136200. PMID 11290735.
  14. ^ van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, Reuser A, Sampson J, Halley D, van der Sluijs P (June 1998). "Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products". Human Molecular Genetics. 7 (6): 1053–7. doi:10.1093/hmg/7.6.1053. PMID 9580671.
  15. ^ Nellist M, Goedbloed MA, de Winter C, Verhaaf B, Jankie A, Reuser AJ, van den Ouweland AM, van der Sluijs P, Halley DJ (October 2002). "Identification and characterization of the interaction between tuberin and 14-3-3zeta". The Journal of Biological Chemistry. 277 (42): 39417–24. doi:10.1074/jbc.M204802200. PMID 12176984.
  16. ^ Li Y, Inoki K, Guan KL (September 2004). "Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity". Molecular and Cellular Biology. 24 (18): 7965–75. doi:10.1128/MCB.24.18.7965-7975.2004. PMC 515062. PMID 15340059.
  17. ^ Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS (February 2003). "The tuberin-hamartin complex negatively regulates beta-catenin signaling activity". The Journal of Biological Chemistry. 278 (8): 5947–51. doi:10.1074/jbc.C200473200. PMID 12511557.
  18. ^ Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP (April 2005). "Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis". Cell. 121 (2): 179–93. doi:10.1016/j.cell.2005.02.031. PMID 15851026. S2CID 18663447.
  19. ^ Cai SL, Tee AR, Short JD, Bergeron JM, Kim J, Shen J, Guo R, Johnson CL, Kiguchi K, Walker CL (April 2006). "Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning". The Journal of Cell Biology. 173 (2): 279–89. doi:10.1083/jcb.200507119. PMC 2063818. PMID 16636147.
  20. ^ Cao Y, Kamioka Y, Yokoi N, Kobayashi T, Hino O, Onodera M, Mochizuki N, Nakae J (December 2006). "Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway". The Journal of Biological Chemistry. 281 (52): 40242–51. doi:10.1074/jbc.M608116200. PMID 17077083.
  21. ^ Inoki K, Zhu T, Guan KL (November 2003). "TSC2 mediates cellular energy response to control cell growth and survival". Cell. 115 (5): 577–90. doi:10.1016/S0092-8674(03)00929-2. PMID 14651849. S2CID 18173817.
  22. ^ Nellist M, Burgers PC, van den Ouweland AM, Halley DJ, Luider TM (August 2005). "Phosphorylation and binding partner analysis of the TSC1-TSC2 complex". Biochemical and Biophysical Research Communications. 333 (3): 818–26. doi:10.1016/j.bbrc.2005.05.175. PMID 15963462.
  23. ^ Goncharova EA, Goncharov DA, Spaits M, Noonan DJ, Talovskaya E, Eszterhas A, Krymskaya VP (May 2006). "Abnormal growth of smooth muscle-like cells in lymphangioleiomyomatosis: Role for tumor suppressor TSC2". American Journal of Respiratory Cell and Molecular Biology. 34 (5): 561–72. doi:10.1165/rcmb.2005-0300OC. PMC 2644221. PMID 16424383.
  24. ^ Astrinidis A, Senapedis W, Coleman TR, Henske EP (December 2003). "Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin B". The Journal of Biological Chemistry. 278 (51): 51372–9. doi:10.1074/jbc.M303956200. PMID 14551205.
  25. ^ Nellist M, Verhaaf B, Goedbloed MA, Reuser AJ, van den Ouweland AM, Halley DJ (December 2001). "TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex". Human Molecular Genetics. 10 (25): 2889–98. doi:10.1093/hmg/10.25.2889. PMID 11741832.
  26. ^ Benvenuto G, Li S, Brown SJ, Braverman R, Vass WC, Cheadle JP, Halley DJ, Sampson JR, Wienecke R, DeClue JE (December 2000). "The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination". Oncogene. 19 (54): 6306–16. doi:10.1038/sj.onc.1204009. PMID 11175345.
  27. ^ Murthy V, Haddad LA, Smith N, Pinney D, Tyszkowski R, Brown D, Ramesh V (May 2000). "Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney". American Journal of Physiology. Renal Physiology. 278 (5): F737–46. doi:10.1152/ajprenal.2000.278.5.F737. PMID 10807585.
  28. ^ Miloloza A, Rosner M, Nellist M, Halley D, Bernaschek G, Hengstschläger M (July 2000). "The TSC1 gene product, hamartin, negatively regulates cell proliferation". Human Molecular Genetics. 9 (12): 1721–7. doi:10.1093/hmg/9.12.1721. PMID 10915759.

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