The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

PPP1R13B  -  protein phosphatase 1, regulatory subunit 13B

Homo sapiens

Synonyms: ASPP1, Apoptosis-stimulating of p53 protein 1, KIAA0771, Protein phosphatase 1 regulatory subunit 13B, p53BP2-like, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of PPP1R13B

  • The expression of ASPP is frequently downregulated in human breast carcinomas expressing wild-type p53 but not mutant p53 [1].
  • ASPP1, a common activator of TP53, is inactivated by aberrant methylation of its promoter in acute lymphoblastic leukemia [2].
  • All four members of this kappa B-specific protein family are structurally related to the v-Rel oncoprotein and one, p85, appears identical to human c-Rel. v-Rel, but not nontransforming v-Rel mutants, binds to the kappa B enhancer and inhibits NF-kappa B-activated transcription from the IL-2 receptor alpha promoter and HIV-1 LTR [3].
  • Since n-3 PFAs are essential for p85-mediated CNS insulin signaling and selective protection of postsynaptic proteins, these findings have implications for neurodegenerative diseases where synaptic loss is critical, especially AD [4].
  • Toward this end, we constructed transgenic potato plants that expressed the ADPG-cleaving adenosine diphosphate sugar pyrophosphatase (ASPP) from Escherichia coli either in the chloroplast or in the cytosol [5].
 

Psychiatry related information on PPP1R13B

  • For this reason, messenger RNA expression of three G protein alpha-subunits and of phosphatidylinositol-3 kinase (PI-3 K) regulatory subunit p85 was examined in granulocytes from patients with bipolar or unipolar affective disorder and compared to healthy controls [6].
 

High impact information on PPP1R13B

  • Here we report the cloning of the cDNA for a highly tyrosine-phosphorylated 36-38 kDa protein, previously characterized by its association with Grb2, phospholipase C-gamma1, and the p85 subunit of phosphoinositide 3-kinase [7].
  • Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases [8].
  • Involvement of p85 in p53-dependent apoptotic response to oxidative stress [9].
  • We report here that the protein p85, a regulator of the signalling protein phosphatidyl-3-OH kinase (PI(3)K), participates in the cell death process that is induced in response to oxidative stress and that this role of p85 in apoptosis does not involve PI(3)K [9].
  • Recent crystallographically derived structures of the Src SH2 domain in complex with low-affinity peptides, which do not contain the EEI consensus, and NMR-derived structures of unliganded Abl (ref. 19) and p85 (ref. 20) SH2 domains have revealed the conserved fold of the SH2 domain and the properties of a phosphotyrosine binding pocket [10].
 

Chemical compound and disease context of PPP1R13B

  • Polyomavirus middle T antigen transforms cells in a manner depending on association of its tyrosine 315 phosphorylation site with Src homology 2 (SH2) domains on the p85 subunit of the phosphatidylinositol 3-kinase [11].
  • Screening of tumor tissues using our method showed that none of malignant gliomas and half of the NF2-related tumors had altered p85 and merlin [12].
  • The secreted p85 glycoprotein was active at a concentration of 120 pM to produce growth-arrest and spindleoid differentiation of murine melanoma F10.9 cells, which do not respond to IL-6 alone [13].
 

Biological context of PPP1R13B

  • Two tumor-derived p53 mutants with reduced apoptotic function were defective in cooperating with ASPP in apoptosis induction [1].
  • ASPP enhance the DNA binding and transactivation function of p53 on the promoters of proapoptotic genes in vivo [1].
  • We show that disruption of p85 by homologous recombination impairs the cellular apoptotic response to oxidative stress [9].
  • We propose that p85 acts as a signal transducer in the cellular response to oxidative stress, mediating cell death regulated by p53 [9].
  • Our results demonstrate that decreased expression of ASPP1 in patients with ALL is due to an abnormal methylation of its promoter and is associated with a poor prognosis [2].
 

Anatomical context of PPP1R13B

  • In the human testis, full-length endogenous hASPP1 protein is located in the nucleus like SAM68, predominantly within meiotic and postmeiotic cells [14].
  • The tumour-suppressor protein ASPP1 is nuclear in human germ cells and can modulate ratios of CD44 exon V5 spliced isoforms in vivo [14].
  • Downregulated mRNA expression of ASPP and the hypermethylation of the 5'-untranslated region in cancer cell lines retaining wild-type p53 [15].
  • Ligand stimulation of an epidermal growth factor receptor/c-erbB-3 chimera expressed in these cells results in a redistribution of p85 to the cell membrane which is independent of the catalytic activity of the enzyme and the integrity of the actin cytoskeleton [16].
  • Here we show using a green fluorescent protein-tagged p85 subunit that phosphatidylinositol 3-kinase is distributed throughout the cytoplasm and is localized to focal adhesion complexes in resting NIH-3T3, A431, and MCF-7 cells [16].
 

Associations of PPP1R13B with chemical compounds

  • The p85 regulatory subunit of phosphatidylinositol 3-kinase, which activates a series of serine kinases, bound to phosphorylated STAT3 and subsequently underwent tyrosine phosphorylation [17].
  • Insulin stimulation of glucose-disposal correlated with association of p85 with IRS-1 [18].
  • Related GAP domains in inositol polyphosphate 5-phosphatase and the p85 subunit of phosphatidylinositol 3-kinase [19].
  • Under basal conditions, transfects demonstrated no expression of p85 or Deltap85, but expression was briskly induced by treatment of the cells with IPTG (EC50 13.7 microM) [20].
  • The p85-associated phosphatidylinositol (PI) 3-kinase/Akt pathway mediates the oestradiol-induced S-phase entry and cyclin D1 promoter activity in MCF-7 cells [21].
 

Regulatory relationships of PPP1R13B

  • ASPP proteins specifically stimulate the apoptotic function of p53 [1].
  • The data showed that mRNA expression of ASPP1 and ASPP2 is downregulated and CpG island tested is hypermethylated [15].
 

Other interactions of PPP1R13B

  • Therefore, ASPP regulate the tumor suppression function of p53 in vivo [1].
  • ASPP1 is a protein homologous to 53BP2, the C-terminal half of ASPP2 [1].
  • Overexpression or deregulation of E2F-1 increased the expression levels of ASPP1 and ASPP2 mRNA and proteins [22].
  • These are the E2F family, the ASPP family, Y-box-binding protein YB1, and the prolyl isomerase Pin1 [23].
  • We have detected a novel protein interaction between the human ASPP1 (hASPP1) protein and the predominantly nuclear adaptor protein SAM68 [14].
 

Analytical, diagnostic and therapeutic context of PPP1R13B

  • Finally, ASPP1 and ASPP2, molecules involved in mediating the transcription function of p53, were not found to be aberrantly expressed when tested by Northern blot analysis [24].
  • Surface plasmon resonance and molecular modeling identified the phosphorylated-Y(71) residue of a p85-binding pYXXM motif in the first sst2 intracellular loop, and p85 COOH-terminal SH2 as direct interacting domains [25].
  • The CD and fluorescence spectroscopy data support the secondary structure prediction based on sequence analysis and provide evidence for flexible linker regions between the various domains of the p85 proteins [26].
  • The membrane-distal region, which contains the major sites of tyrosine phosphorylation, is required for phosphorylation of SHC and p85, not for mitogenesis, thus allowing functional dissection of the signaling pathways activated by cytokines [27].
  • Western blot (immunoblot) analyses using an anti-p85 polyclonal antibody and a specific anti-p85/AS53 antibody confirmed the tissue distribution of p85/AS53 protein and indicate a approximately 7-fold higher expression of p85/AS53 protein than of p85 in skeletal muscle [28].

References

  1. ASPP proteins specifically stimulate the apoptotic function of p53. Samuels-Lev, Y., O'Connor, D.J., Bergamaschi, D., Trigiante, G., Hsieh, J.K., Zhong, S., Campargue, I., Naumovski, L., Crook, T., Lu, X. Mol. Cell (2001) [Pubmed]
  2. ASPP1, a common activator of TP53, is inactivated by aberrant methylation of its promoter in acute lymphoblastic leukemia. Agirre, X., Román-Gómez, J., Jiménez-Velasco, A., Garate, L., Montiel-Duarte, C., Navarro, G., Vázquez, I., Zalacain, M., Calasanz, M.J., Heiniger, A., Torres, A., Minna, J.D., Prósper, F. Oncogene (2006) [Pubmed]
  3. The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF-kappa B function. Ballard, D.W., Walker, W.H., Doerre, S., Sista, P., Molitor, J.A., Dixon, E.P., Peffer, N.J., Hannink, M., Greene, W.C. Cell (1990) [Pubmed]
  4. Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Calon, F., Lim, G.P., Yang, F., Morihara, T., Teter, B., Ubeda, O., Rostaing, P., Triller, A., Salem, N., Ashe, K.H., Frautschy, S.A., Cole, G.M. Neuron (2004) [Pubmed]
  5. Most of ADP x glucose linked to starch biosynthesis occurs outside the chloroplast in source leaves. Baroja-Fernández, E., Muñoz, F.J., Zandueta-Criado, A., Morán-Zorzano, M.T., Viale, A.M., Alonso-Casajús, N., Pozueta-Romero, J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  6. Abnormal G protein alpha(s) - and alpha(i2)-subunit mRNA expression in bipolar affective disorder. Spleiss, O., van Calker, D., Schärer, L., Adamovic, K., Berger, M., Gebicke-Haerter, P.J. Mol. Psychiatry (1998) [Pubmed]
  7. LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Zhang, W., Sloan-Lancaster, J., Kitchen, J., Trible, R.P., Samelson, L.E. Cell (1998) [Pubmed]
  8. Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases. Skolnik, E.Y., Margolis, B., Mohammadi, M., Lowenstein, E., Fischer, R., Drepps, A., Ullrich, A., Schlessinger, J. Cell (1991) [Pubmed]
  9. Involvement of p85 in p53-dependent apoptotic response to oxidative stress. Yin, Y., Terauchi, Y., Solomon, G.G., Aizawa, S., Rangarajan, P.N., Yazaki, Y., Kadowaki, T., Barrett, J.C. Nature (1998) [Pubmed]
  10. Recognition of a high-affinity phosphotyrosyl peptide by the Src homology-2 domain of p56lck. Eck, M.J., Shoelson, S.E., Harrison, S.C. Nature (1993) [Pubmed]
  11. Genetic analysis of a phosphatidylinositol 3-kinase SH2 domain reveals determinants of specificity. Yoakim, M., Hou, W., Songyang, Z., Liu, Y., Cantley, L., Schaffhausen, B. Mol. Cell. Biol. (1994) [Pubmed]
  12. Loss of merlin-p85 protein complex in NF2-related tumors. Takeshima, H., Nishi, T., Yamamoto, K., Kino, T., Nakamura, H., Saya, H., Kochi, M., Kuratsu, J.I., Ushio, Y. Int. J. Oncol. (1998) [Pubmed]
  13. Interleukin-6 receptor-interleukin-6 fusion proteins with enhanced interleukin-6 type pleiotropic activities. Chebath, J., Fischer, D., Kumar, A., Oh, J.W., Kolett, O., Lapidot, T., Fischer, M., Rose-John, S., Nagler, A., Slavin, S., Revel, M. Eur. Cytokine Netw. (1997) [Pubmed]
  14. The tumour-suppressor protein ASPP1 is nuclear in human germ cells and can modulate ratios of CD44 exon V5 spliced isoforms in vivo. Thornton, J.K., Dalgleish, C., Venables, J.P., Sergeant, K.A., Ehrmann, I.E., Lu, X., Saunders, P.T., Elliott, D.J. Oncogene (2006) [Pubmed]
  15. Downregulated mRNA expression of ASPP and the hypermethylation of the 5'-untranslated region in cancer cell lines retaining wild-type p53. Liu, Z.J., Lu, X., Zhang, Y., Zhong, S., Gu, S.Z., Zhang, X.B., Yang, X., Xin, H.M. FEBS Lett. (2005) [Pubmed]
  16. Intracellular movement of green fluorescent protein-tagged phosphatidylinositol 3-kinase in response to growth factor receptor signaling. Gillham, H., Golding, M.C., Pepperkok, R., Gullick, W.J. J. Cell Biol. (1999) [Pubmed]
  17. STAT3 as an adapter to couple phosphatidylinositol 3-kinase to the IFNAR1 chain of the type I interferon receptor. Pfeffer, L.M., Mullersman, J.E., Pfeffer, S.R., Murti, A., Shi, W., Yang, C.H. Science (1997) [Pubmed]
  18. Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. Cusi, K., Maezono, K., Osman, A., Pendergrass, M., Patti, M.E., Pratipanawatr, T., DeFronzo, R.A., Kahn, C.R., Mandarino, L.J. J. Clin. Invest. (2000) [Pubmed]
  19. Related GAP domains in inositol polyphosphate 5-phosphatase and the p85 subunit of phosphatidylinositol 3-kinase. Baldwin, G.S., Zhang, Q.X. Trends Biochem. Sci. (1993) [Pubmed]
  20. Receptor-mediated endocytosis of albumin by kidney proximal tubule cells is regulated by phosphatidylinositide 3-kinase. Brunskill, N.J., Stuart, J., Tobin, A.B., Walls, J., Nahorski, S. J. Clin. Invest. (1998) [Pubmed]
  21. PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells. Castoria, G., Migliaccio, A., Bilancio, A., Di Domenico, M., de Falco, A., Lombardi, M., Fiorentino, R., Varricchio, L., Barone, M.V., Auricchio, F. EMBO J. (2001) [Pubmed]
  22. ASPP1 and ASPP2 are new transcriptional targets of E2F. Fogal, V., Kartasheva, N.N., Trigiante, G., Llanos, S., Yap, D., Vousden, K.H., Lu, X. Cell Death Differ. (2005) [Pubmed]
  23. Some p53-binding proteins that can function as arbiters of life and death. Braithwaite, A.W., Del Sal, G., Lu, X. Cell Death Differ. (2006) [Pubmed]
  24. p53 apoptotic pathway molecules are frequently and simultaneously altered in nonsmall cell lung carcinoma. Mori, S., Ito, G., Usami, N., Yoshioka, H., Ueda, Y., Kodama, Y., Takahashi, M., Fong, K.M., Shimokata, K., Sekido, Y. Cancer (2004) [Pubmed]
  25. Direct binding of p85 to sst2 somatostatin receptor reveals a novel mechanism for inhibiting PI3K pathway. Bousquet, C., Guillermet-Guibert, J., Saint-Laurent, N., Archer-Lahlou, E., Lopez, F., Fanjul, M., Ferrand, A., Fourmy, D., Pichereaux, C., Monsarrat, B., Pradayrol, L., Estève, J.P., Susini, C. EMBO J. (2006) [Pubmed]
  26. Interaction of the p85 subunit of PI 3-kinase and its N-terminal SH2 domain with a PDGF receptor phosphorylation site: structural features and analysis of conformational changes. Panayotou, G., Bax, B., Gout, I., Federwisch, M., Wroblowski, B., Dhand, R., Fry, M.J., Blundell, T.L., Wollmer, A., Waterfield, M.D. EMBO J. (1992) [Pubmed]
  27. Jaks and Stats in signaling by the cytokine receptor superfamily. Ihle, J.N., Kerr, I.M. Trends Genet. (1995) [Pubmed]
  28. Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain. Antonetti, D.A., Algenstaedt, P., Kahn, C.R. Mol. Cell. Biol. (1996) [Pubmed]
 
WikiGenes - Universities