Sequestosome-1 is a protein that in humans is encoded by the SQSTM1 gene.[1][2][3] Also known as the ubiquitin-binding protein p62,[4] it is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy. By interacting with GATA4 and targeting it for degradation, it can inhibit GATA-4 associated senescence and senescence-associated secretory phenotype.[5]

Mutations in SQSTM1 are a common cause of Paget's disease of bone.[6]

Interactions

Sequestosome 1 has been shown to interact with:

Role in cancer

The SQSTM1 gene, which is actively transcribed as part of normal cellular function, is sometimes identified in fusion proteins, which can cause cancer when SQSTM1 is abnormally fused to a tyrosine kinase or other pro-proliferation gene. These genes are normally tightly regulated, but when bound to a minimally regulated gene like SQSTM1, they cause abnormal over-expression.[17]

References

  1. ^ Joung I, Strominger JL, Shin J (July 1996). "Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain". Proceedings of the National Academy of Sciences of the United States of America. 93 (12): 5991–5995. Bibcode:1996PNAS...93.5991J. doi:10.1073/pnas.93.12.5991. PMC 39176. PMID 8650207
  2. ^ Devergne O, Hummel M, Koeppen H, Le Beau MM, Nathanson EC, Kieff E, Birkenbach M (February 1996). "A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes". Journal of Virology. 70 (2): 1143–1153. doi:10.1128/JVI.70.2.1143-1153.1996. PMC 189923. PMID 8551575
  3. ^ "Entrez Gene: SQSTM1 sequestosome 1"
  4. ^
  5. ^ Cassidy LD, Narita M (Sep 2015). "GATA get a hold on senescence". Science. 349 (6255): 1448–1449. Bibcode:2015Sci...349.1448C. doi:10.1126/science.aad2501. PMID 26404812. S2CID 35805331
  6. ^ Layfield R, Ciani B, Ralston S, Hocking L, Sheppard P, Searle M, Cavey J (2004-10-26). "Structural and functional studies of mutations affecting the UBA domain of SQSTM1 (p62) which cause Paget's disease of bone". Biochemical Society Transactions. 32 (Pt 5): 728–730. doi:10.1042/bst0320728. ISSN 0300-5127. PMID 15493999. S2CID 22544044
  7. ^ Shvets E, Fass E, Scherz-Shouval R, Elazar Z (August 2008). "The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes". Journal of Cell Science. 121 (Pt 16): 2685–2695. doi:10.1242/jcs.026005. PMID 18653543. S2CID 2782335
  8. ^ Sanchez P, De Carcer G, Sandoval IV, Moscat J, Diaz-Meco MT (May 1998). "Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62". Molecular and Cellular Biology. 18 (5): 3069–3080. doi:10.1128/mcb.18.5.3069. PMC 110686. PMID 9566925
  9. ^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026
  10. ^ Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J (Jun 1999). "The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation". The EMBO Journal. 18 (11): 3044–3053. doi:10.1093/emboj/18.11.3044. PMC 1171386. PMID 10356400
  11. ^ Sanz L, Diaz-Meco MT, Nakano H, Moscat J (April 2000). "The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway". The EMBO Journal. 19 (7): 1576–1586. doi:10.1093/emboj/19.7.1576. PMC 310227. PMID 10747026
  12. ^ Wooten MW, Seibenhener ML, Mamidipudi V, Diaz-Meco MT, Barker PA, Moscat J (March 2001). "The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor". Journal of Biological Chemistry. 276 (11): 7709–7712. doi:10.1074/jbc.C000869200. PMID 11244088
  13. ^ Geetha T, Wooten MW (February 2003). "Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling". Journal of Biological Chemistry. 278 (7): 4730–4739. doi:10.1074/jbc.M208468200. PMID 12471037
  14. ^ Jadhav T, Geetha T, Jiang J, Wooten MW (Jul 2008). "Identification of a consensus site for TRAF6/p62 polyubiquitination". Biochemical and Biophysical Research Communications. 371 (3): 521–524. Bibcode:2008BBRC..371..521J. doi:10.1016/j.bbrc.2008.04.138. PMC 2474794. PMID 18457658
  15. ^ Wooten MW, Geetha T, Babu JR, Seibenhener ML, Peng J, Cox N, Diaz-Meco MT, Moscat J (March 2008). "Essential role of sequestosome 1/p62 in regulating accumulation of Lys63-ubiquitinated proteins". Journal of Biological Chemistry. 283 (11): 6783–6789. doi:10.1074/jbc.M709496200. PMID 18174161
  16. ^ Feng, Lifeng et al. "Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia" Theranostics vol. 7,7 1890-1900. 10 Apr. 2017, doi:10.7150/thno.19135
  17. ^ Badiu DC, Ploscaru IC, Zgura A, Bacinschi X, Smarandache CG, Serban D, Popescu CG, Grigorean VT, Botnarciuc V, Manea CA (July 2022). "A review of NTRK fusions in cancer". Annals of Medicine and Surgery. 79. doi:10.1016/j.amsu.2022.103893. ISSN 2049-0801. PMC 9289232. PMID 35860155

Further reading

  • Geetha T, Wooten MW (Feb 2002). "Structure and functional properties of the ubiquitin binding protein p62". FEBS Letters. 512 (1–3): 19–24. Bibcode:2002FEBSL.512...19G. doi:10.1016/S0014-5793(02)02286-X. PMID 11852044. S2CID 22029085
  • Layfield R, Ciani B, Ralston SH, Hocking LJ, Sheppard PW, Searle MS, Cavey JR (Nov 2004). "Structural and functional studies of mutations affecting the UBA domain of SQSTM1 (p62) which cause Paget's disease of bone". Biochemical Society Transactions. 32 (Pt 5): 728–730. doi:10.1042/BST0320728. PMID 15493999. S2CID 22544044
  • Michou L, Collet C, Laplanche JL, Orcel P, Cornélis F (May 2006). "Genetics of Paget's disease of bone". Joint Bone Spine. 73 (3): 243–248. doi:10.1016/j.jbspin.2005.05.009. PMID 16574459
  • Park I, Chung J, Walsh CT, Yun Y, Strominger JL, Shin J (Dec 1995). "Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region". Proceedings of the National Academy of Sciences of the United States of America. 92 (26): 12338–12342. doi:10.1073/pnas.92.26.12338. PMC 40352. PMID 8618896
  • Iyer N, Reagan MS, Wu KJ, Canagarajah B, Friedberg EC (Feb 1996). "Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein". Biochemistry. 35 (7): 2157–2167. doi:10.1021/bi9524124. PMID 8652557
  • Vadlamudi RK, Joung I, Strominger JL, Shin J (Aug 1996). "p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins". Journal of Biological Chemistry. 271 (34): 20235–20237. doi:10.1074/jbc.271.34.20235. PMID 8702753
  • Marcus SL, Winrow CJ, Capone JP, Rachubinski RA (Nov 1996). "A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor". Journal of Biological Chemistry. 271 (44): 27197–27200. doi:10.1074/jbc.271.44.27197. PMID 8910285
  • Jallal B, Mossie K, Vasiloudis G, Knyazev P, Zachwieja J, Clairvoyant F, Schilling J, Ullrich A (May 1997). "The receptor-like protein-tyrosine phosphatase DEP-1 is constitutively associated with a 64-kDa protein serine/threonine kinase". Journal of Biological Chemistry. 272 (18): 12158–12163. doi:10.1074/jbc.272.18.12158. PMID 9115287
  • Sanchez P, De Carcer G, Sandoval IV, Moscat J, Diaz-Meco MT (May 1998). "Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62". Molecular and Cellular Biology. 18 (5): 3069–3080. doi:10.1128/mcb.18.5.3069. PMC 110686. PMID 9566925
  • Vadlamudi RK, Shin J (Sep 1998). "Genomic structure and promoter analysis of the p62 gene encoding a non-proteasomal multiubiquitin chain binding protein". FEBS Letters. 435 (2–3): 138–142. Bibcode:1998FEBSL.435..138V. doi:10.1016/S0014-5793(98)01021-7. PMID 9762895. S2CID 3184369
  • Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J (Jun 1999). "The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation". The EMBO Journal. 18 (11): 3044–3053. doi:10.1093/emboj/18.11.3044. PMC 1171386. PMID 10356400
  • Stumptner C, Heid H, Fuchsbichler A, Hauser H, Mischinger HJ, Zatloukal K, Denk H (Jun 1999). "Analysis of intracytoplasmic hyaline bodies in a hepatocellular carcinoma. Demonstration of p62 as major constituent". The American Journal of Pathology. 154 (6): 1701–1710. doi:10.1016/S0002-9440(10)65426-0. PMC 1866621. PMID 10362795
  • Sudo T, Maruyama M, Osada H (Mar 2000). "p62 functions as a p38 MAP kinase regulator". Biochemical and Biophysical Research Communications. 269 (2): 521–525. Bibcode:2000BBRC..269..521S. doi:10.1006/bbrc.2000.2333. PMID 10708586
  • Sanz L, Diaz-Meco MT, Nakano H, Moscat J (Apr 2000). "The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway". The EMBO Journal. 19 (7): 1576–1586. doi:10.1093/emboj/19.7.1576. PMC 310227. PMID 10747026
  • Wooten MW, Seibenhener ML, Mamidipudi V, Diaz-Meco MT, Barker PA, Moscat J (Mar 2001). "The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor". Journal of Biological Chemistry. 276 (11): 7709–7712. doi:10.1074/jbc.C000869200. PMID 11244088
  • Kuusisto E, Salminen A, Alafuzoff I (Jul 2001). "Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies". NeuroReport. 12 (10): 2085–2090. doi:10.1097/00001756-200107200-00009. PMID 11447312. S2CID 21272705
  • Laurin N, Brown JP, Lemainque A, Duchesne A, Huot D, Lacourcière Y, Drapeau G, Verreault J, Raymond V, Morissette J (Sep 2001). "Paget disease of bone: mapping of two loci at 5q35-qter and 5q31". American Journal of Human Genetics. 69 (3): 528–543. doi:10.1086/322975. PMC 1235483. PMID 11473345
  • Chang S, Kim JH, Shin J (Jan 2002). "p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition". FEBS Letters. 510 (1–2): 57–61. Bibcode:2002FEBSL.510...57C. doi:10.1016/S0014-5793(01)03224-0. PMID 11755531. S2CID 85579338
  • Feng L, Li J, Yang L, Zhu L, Huang X, Zhang S, Luo L, Jiang Z, Jiang T, Xu W, Wang X, Jin H (2017). "Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia". Theranostics. 7 (7): 1890–1900. doi:10.7150/thno.19135. PMC 5479276. PMID 28638475