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Gene Review

Sqstm1  -  sequestosome 1

Mus musculus

Synonyms: A170, OSF-6, Osi, STAP, STONE14, ...
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Disease relevance of Sqstm1

  • Recently, p62 mutations have been shown to be the cause of the 5q35-linked Paget's disease of bone, a genetic disorder characterized by aberrant osteoclastic activity [1].

High impact information on Sqstm1

  • We suggest that p62 may, via LC3, be involved in linking polyubiquitinated protein aggregates to the autophagy machinery [2].
  • Reduction of p62 protein levels or interference with p62 function significantly increased cell death that was induced by the expression of mutant huntingtin [2].
  • In this study, we report that polymerization of the polyubiquitin-binding protein p62/SQSTM1 yields protein bodies that either reside free in the cytosol and nucleus or occur within autophagosomes and lysosomal structures [2].
  • p62 is a highly tyrosyl phosphorylated protein that was first identified in immunoprecipitates of the GTPase-activating protein (GAP) of p21ras from cells transformed by oncogenic nonreceptor tyrosine kinases or stimulated through tyrosine kinase receptors (C. Ellis, M. Moran, F. McCormick, and T. Pawson, Nature 343:377-381, 1991) [3].
  • This protein corresponds to the major tyrosine-phosphorylated protein that is induced in differentiating keratinocytes as early as 5 min after calcium addition. p62 phosphorylation was not observed after exposure of these cells to epidermal growth factor, phorbol ester, or transforming growth factor beta [4].

Biological context of Sqstm1


Anatomical context of Sqstm1


Associations of Sqstm1 with chemical compounds

  • Furthermore, the level of p62 protein and mRNA was increased in expanded polyglutamine-expressing cells [10].
  • The levels of glucose oxidase-induced A170 protein did not decrease after the addition of cycloheximide [7].
  • Arsenate also markedly increased ubiquitin-conjugated cellular proteins, suggesting that HMM-A170 was one of the poly-ubiquitinated proteins [8].
  • Arsenite (50-100 micro M) also induced accumulation of HMM-A170 and ubiquitin-conjugated proteins [8].
  • We demonstrate here that the expression levels of p62 mRNA and protein were increased in Neuro-2a cells and cultured rat hippocampal neurons by different types of proapoptotic treatments, including serum deprivation, okadaic acid, etoposide, and trichostatin A [11].
  • When p62 was co-expressed with SOD1 in NSC34 cells, it greatly enhanced the formation of aggregates of the ALS-linked SOD1 mutants, but not wild-type SOD1 [12].

Physical interactions of Sqstm1

  • A search of sequence databases revealed that the A170 protein is roughly 90% identical to a human protein that binds to the Src homology 2 domain of the T-cell-specific tyrosine kinase p56lck [13].

Other interactions of Sqstm1


Analytical, diagnostic and therapeutic context of Sqstm1


  1. The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis. Durán, A., Serrano, M., Leitges, M., Flores, J.M., Picard, S., Brown, J.P., Moscat, J., Diaz-Meco, M.T. Dev. Cell (2004) [Pubmed]
  2. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. Bjørkøy, G., Lamark, T., Brech, A., Outzen, H., Perander, M., Overvatn, A., Stenmark, H., Johansen, T. J. Cell Biol. (2005) [Pubmed]
  3. A protein that is highly related to GTPase-activating protein-associated p62 complexes with phospholipase C gamma. Maa, M.C., Leu, T.H., Trandel, B.J., Chang, J.H., Parsons, S.J. Mol. Cell. Biol. (1994) [Pubmed]
  4. Specific changes of Ras GTPase-activating protein (GAP) and a GAP-associated p62 protein during calcium-induced keratinocyte differentiation. Filvaroff, E., Calautti, E., McCormick, F., Dotto, G.P. Mol. Cell. Biol. (1992) [Pubmed]
  5. Cloning, expression profile, and genomic organization of the mouse STAP/A170 gene. Okazaki, M., Ito, S., Kawakita, K., Takeshita, S., Kawai, S., Makishima, F., Oda, H., Kakinuma, A. Genomics (1999) [Pubmed]
  6. Phosphorylation of A170 stress protein by casein kinase II-like activity in macrophages. Yanagawa, T., Yuki, K., Yoshida, H., Bannai, S., Ishii, T. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  7. Low micromolar levels of hydrogen peroxide and proteasome inhibitors induce the 60-kDa A170 stress protein in murine peritoneal macrophages. Ishii, T., Yanagawa, T., Yuki, K., Kawane, T., Yoshida, H., Bannai, S. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  8. Activation of Nrf2 and accumulation of ubiquitinated A170 by arsenic in osteoblasts. Aono, J., Yanagawa, T., Itoh, K., Li, B., Yoshida, H., Kumagai, Y., Yamamoto, M., Ishii, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  9. p62/p56 are cortical granule proteins that contribute to formation of the cortical granule envelope and play a role in mammalian preimplantation development. Hoodbhoy, T., Dandekar, P., Calarco, P., Talbot, P. Mol. Reprod. Dev. (2001) [Pubmed]
  10. Increased expression of p62 in expanded polyglutamine-expressing cells and its association with polyglutamine inclusions. Nagaoka, U., Kim, K., Jana, N.R., Doi, H., Maruyama, M., Mitsui, K., Oyama, F., Nukina, N. J. Neurochem. (2004) [Pubmed]
  11. Ubiquitin-binding protein p62 expression is induced during apoptosis and proteasomal inhibition in neuronal cells. Kuusisto, E., Suuronen, T., Salminen, A. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  12. p62 accumulates and enhances aggregate formation in model systems of familial amyotrophic lateral sclerosis. Gal, J., Ström, A.L., Kilty, R., Zhang, F., Zhu, H. J. Biol. Chem. (2007) [Pubmed]
  13. Murine peritoneal macrophages induce a novel 60-kDa protein with structural similarity to a tyrosine kinase p56lck-associated protein in response to oxidative stress. Ishii, T., Yanagawa, T., Kawane, T., Yuki, K., Seita, J., Yoshida, H., Bannai, S. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  14. A 62-kDa mitotic apparatus protein required for mitotic progression is sequestered to the interphase nucleus by associating with the chromosomes during anaphase. Ye, X., Sloboda, R.D. Cell Motil. Cytoskeleton (1995) [Pubmed]
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