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PSIP1  -  PC4 and SFRS1 interacting protein 1

Homo sapiens

Synonyms: CLL-associated antigen KW-7, DFS 70, DFS70, Dense fine speckles 70 kDa protein, LEDGF, ...
 
 
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Disease relevance of PSIP1

 

Psychiatry related information on PSIP1

 

High impact information on PSIP1

  • Cells expressing a noncleavable mutant of p75 sustain DeltaPsim and ATP levels during apoptosis, and ROS production in response to apoptotic stimuli is dampened [7].
  • Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain [7].
  • While cytochrome c release and DNA fragmentation are unaffected by the noncleavable p75 mutant, mitochondrial morphology of dying cells is maintained, and loss of plasma membrane integrity is delayed [7].
  • Many investigations indicate that the survival-promoting signals of neurotrophins are generated by activation of Trk tyrosine kinase receptors and that their death-promoting signals are generated by activation of p75 neurotrophin receptors (p75(NTR)) [8].
  • We show here that during dendritic cell maturation, rapidly activated dimers (e.g., p50/RelA) bound to a subset of target promoters are gradually replaced by slowly activated dimers (e.g., p52/RelB) [9].
 

Chemical compound and disease context of PSIP1

  • A polypeptide complex (p52) belonging to the Epstein-Barr virus (EBV)-induced early antigen complex (EA) has been isolated from IdU-induced Raji and B95-8 cells as well as from n-butyrate-induced P3HR-1 cells [10].
  • Constitutively tyrosine phosphorylated p52 Shc in breast cancer cells: correlation with ErbB2 and p66 Shc expression [11].
  • Exposure of SN56 cholinergic neuroblastoma cells to dibutyryl cAMP and retinoic acid for 3 days caused their morphologic differentiation along with the increase in choline acetyltransferase activity, acetylcholine content and release, calcium content, and the expression of p75 neurotrophin receptors [12].
  • 3. Kirsten sarcoma virus-transformed NRK cells failed to accumulate p52 in either the secreted or substrate-associated protein compartments; this protein was inducible, however, in transformed cells by culture in 2 mM sodium-n-butyrate [13].
  • Serum antibodies to EBV viral capsid antigen (VCA) IgM and EBV Early Antigen, diffuse (EA, D) as well HVCMV(V), IgM and IgG; VP (sucrose, density purified V); p52 and CM2 IgM serum antibodies were assayed [14].
 

Biological context of PSIP1

 

Anatomical context of PSIP1

 

Associations of PSIP1 with chemical compounds

  • Here, gel-shift and super-shift assays confirm the binding of LEDGF to the DNA fragments containing HSEs and STREs that are present in the involucrin gene promoter [16].
  • Cells treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to stimulate production of H(2)O(2), showed higher levels of LEDGF mRNA [16].
  • A single classical nuclear localization signal (NLS) in the LEDGF/p75 N-terminal region ((146)RRGRKRKAEKQ(156)) was found by deletion mapping and was shown to be transferable to pyruvate kinase [19].
  • We show by deletion mapping that processing of NF-(kappa)B2(p100) terminates at alanine 405 to generate p52 and is prevented by specific inhibitors of the multicatalytic proteinase complex [20].
  • Biochemical analysis showed that full-length LEDGF/p75 resists Triton X-100 extraction from chromatin [21].
 

Physical interactions of PSIP1

  • We found that LEDGF bound to the heat shock element and to stress-related elements in the AOP2 promoter [22].
 

Regulatory relationships of PSIP1

  • In addition, in HCK cell over-expressing LEDGF, the levels of hINV mRNA and hINV protein are increased by four to five-fold [16].
  • Here we provide evidence that TGF-beta1 down-regulates LEDGF expression and diminishes its affinity for DNA during TGF-beta1-induced phenotypic changes and apoptosis in human lens epithelial cells [23].
 

Other interactions of PSIP1

  • Biochemical and genetic analyses of integrase-interacting proteins lens epithelium-derived growth factor (LEDGF)/p75 and hepatoma-derived growth factor related protein 2 (HRP2) in preintegration complex function and HIV-1 replication [24].
  • A novel transcriptional coactivator, p52, functionally interacts with the essential splicing factor ASF/SF2 [15].
  • This regulation appears to be physiologically important, as over-expression of HCK with LEDGF increases the expression of the endogenous hINV gene and may provide new insight to understand the molecular mechanism of transcriptional regulation of this gene [16].
  • We describe here a case of CML who presented de novo in transformation with a t(9;11)(p21;p15) and NUP98-LEDGF fusion in addition to the t(9;22) [25].
  • Caspase cleavage of the nuclear autoantigen LEDGF/p75 abrogates its pro-survival function: implications for autoimmunity in atopic disorders [17].
 

Analytical, diagnostic and therapeutic context of PSIP1

References

  1. Identification of an evolutionarily conserved domain in human lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF/p75) that binds HIV-1 integrase. Cherepanov, P., Devroe, E., Silver, P.A., Engelman, A. J. Biol. Chem. (2004) [Pubmed]
  2. Disruption of ledgf/psip1 results in perinatal mortality and homeotic skeletal transformations. Sutherland, H.G., Newton, K., Brownstein, D.G., Holmes, M.C., Kress, C., Semple, C.A., Bickmore, W.A. Mol. Cell. Biol. (2006) [Pubmed]
  3. Identification and characterization of a functional nuclear localization signal in the HIV-1 integrase interactor LEDGF/p75. Maertens, G., Cherepanov, P., Debyser, Z., Engelborghs, Y., Engelman, A. J. Biol. Chem. (2004) [Pubmed]
  4. Lens epithelium-derived growth factor/p75 prevents proteasomal degradation of HIV-1 integrase. Llano, M., Delgado, S., Vanegas, M., Poeschla, E.M. J. Biol. Chem. (2004) [Pubmed]
  5. The interaction of LEDGF/p75 with integrase is lentivirus-specific and promotes DNA binding. Busschots, K., Vercammen, J., Emiliani, S., Benarous, R., Engelborghs, Y., Christ, F., Debyser, Z. J. Biol. Chem. (2005) [Pubmed]
  6. Regulation of p53 tumour suppressor target gene expression by the p52 NF-kappaB subunit. Schumm, K., Rocha, S., Caamano, J., Perkins, N.D. EMBO J. (2006) [Pubmed]
  7. Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain. Ricci, J.E., Muñoz-Pinedo, C., Fitzgerald, P., Bailly-Maitre, B., Perkins, G.A., Yadava, N., Scheffler, I.E., Ellisman, M.H., Green, D.R. Cell (2004) [Pubmed]
  8. The protean actions of neurotrophins and their receptors on the life and death of neurons. Kalb, R. Trends Neurosci. (2005) [Pubmed]
  9. Modulation of NF-kappaB activity by exchange of dimers. Saccani, S., Pantano, S., Natoli, G. Mol. Cell (2003) [Pubmed]
  10. Purification of a polypeptide complex (p52) belonging to the D-subspecificites of Epstein-Barr virus-induced early antigens. Dölken, G., Hecht, T., Weitzmann, U., Wagner, M., Löhr, G.W., Hirsch, F.W. Virology (1986) [Pubmed]
  11. Constitutively tyrosine phosphorylated p52 Shc in breast cancer cells: correlation with ErbB2 and p66 Shc expression. Stevenson, L.E., Frackelton, A.R. Breast Cancer Res. Treat. (1998) [Pubmed]
  12. Phenotype-dependent susceptibility of cholinergic neuroblastoma cells to neurotoxic inputs. Szutowicz, A., Bielarczyk, H., Gul, S., Ronowska, A., Pawe??czyk, T., Jankowska-Kulawy, A. Metabolic brain disease (2006) [Pubmed]
  13. Sodium-n-butyrate induces secretion and substrate accumulation of p52 in Kirsten sarcoma virus-transformed rat kidney fibroblasts. Ryan, M.P., Higgins, P.J. Int. J. Biochem. (1989) [Pubmed]
  14. IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with the chronic fatigue syndrome. Lerner, A.M., Beqaj, S.H., Deeter, R.G., Fitzgerald, J.T. In Vivo (2004) [Pubmed]
  15. A novel transcriptional coactivator, p52, functionally interacts with the essential splicing factor ASF/SF2. Ge, H., Si, Y., Wolffe, A.P. Mol. Cell (1998) [Pubmed]
  16. Transactivation of involucrin, a marker of differentiation in keratinocytes, by lens epithelium-derived growth factor (LEDGF). Kubo, E., Fatma, N., Sharma, P., Shinohara, T., Chylack, L.T., Akagi, Y., Singh, D.P. J. Mol. Biol. (2002) [Pubmed]
  17. Caspase cleavage of the nuclear autoantigen LEDGF/p75 abrogates its pro-survival function: implications for autoimmunity in atopic disorders. Wu, X., Daniels, T., Molinaro, C., Lilly, M.B., Casiano, C.A. Cell Death Differ. (2002) [Pubmed]
  18. Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virus. Vandekerckhove, L., Christ, F., Van Maele, B., De Rijck, J., Gijsbers, R., Van den Haute, C., Witvrouw, M., Debyser, Z. J. Virol. (2006) [Pubmed]
  19. Identification of the LEDGF/p75 HIV-1 integrase-interaction domain and NLS reveals NLS-independent chromatin tethering. Vanegas, M., Llano, M., Delgado, S., Thompson, D., Peretz, M., Poeschla, E. J. Cell. Sci. (2005) [Pubmed]
  20. Differential regulation of NF-kappaB2(p100) processing and control by amino-terminal sequences. Betts, J.C., Nabel, G.J. Mol. Cell. Biol. (1996) [Pubmed]
  21. Identification and characterization of the chromatin-binding domains of the HIV-1 integrase interactor LEDGF/p75. Llano, M., Vanegas, M., Hutchins, N., Thompson, D., Delgado, S., Poeschla, E.M. J. Mol. Biol. (2006) [Pubmed]
  22. Transcriptional regulation of the antioxidant protein 2 gene, a thiol-specific antioxidant, by lens epithelium-derived growth factor to protect cells from oxidative stress. Fatma, N., Singh, D.P., Shinohara, T., Chylack, L.T. J. Biol. Chem. (2001) [Pubmed]
  23. Lens epithelium-derived growth factor relieves transforming growth factor-beta1-induced transcription repression of heat shock proteins in human lens epithelial cells. Sharma, P., Fatma, N., Kubo, E., Shinohara, T., Chylack, L.T., Singh, D.P. J. Biol. Chem. (2003) [Pubmed]
  24. Biochemical and genetic analyses of integrase-interacting proteins lens epithelium-derived growth factor (LEDGF)/p75 and hepatoma-derived growth factor related protein 2 (HRP2) in preintegration complex function and HIV-1 replication. Vandegraaff, N., Devroe, E., Turlure, F., Silver, P.A., Engelman, A. Virology (2006) [Pubmed]
  25. NUP98-LEDGF fusion and t(9;11) in transformed chronic myeloid leukemia. Grand, F.H., Koduru, P., Cross, N.C., Allen, S.L. Leuk. Res. (2005) [Pubmed]
  26. Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions. Ochs, R.L., Muro, Y., Si, Y., Ge, H., Chan, E.K., Tan, E.M. J. Allergy Clin. Immunol. (2000) [Pubmed]
  27. Autoantibodies to DFS70/LEDGF are increased in alopecia areata patients. Okamoto, M., Ogawa, Y., Watanabe, A., Sugiura, K., Shimomura, Y., Aoki, N., Nagasaka, T., Tomita, Y., Muro, Y. J. Autoimmun. (2004) [Pubmed]
  28. Autoantigenicity of DFS70 is restricted to the conformational epitope of C-terminal alpha-helical domain. Ogawa, Y., Sugiura, K., Watanabe, A., Kunimatsu, M., Mishima, M., Tomita, Y., Muro, Y. J. Autoimmun. (2004) [Pubmed]
  29. Lens epithelium-derived growth factor (LEDGF/p75) expression in fetal and adult human brain. Chylack, L.T., Fu, L., Mancini, R., Martin-Rehrmann, M.D., Saunders, A.J., Konopka, G., Tian, D., Hedley-Whyte, E.T., Folkerth, R.D., Goldstein, L.E. Exp. Eye Res. (2004) [Pubmed]
 
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