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CREG1  -  cellular repressor of E1A-stimulated genes 1

Homo sapiens

Synonyms: CREG, Cellular repressor of E1A-stimulated genes 1, Protein CREG1, UNQ727/PRO1409
 
 
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Disease relevance of CREG1

 

High impact information on CREG1

  • Thus, analysis of a structure-based mutant of CREG revealed that binding to M6P/IGF2R, while necessary, is not sufficient for CREG-induced growth suppression [2].
  • The crystal structure of CREG, a secreted glycoprotein involved in cellular growth and differentiation [2].
  • Our structure shows that the putative flavin mononucleotide-binding pocket in CREG is sterically blocked by a loop and several key bulky residues [2].
  • A mutant of CREG lacking a part of this loop maintained overall structure and dimerization, as well as M6P/IGF2R binding, but lost the growth suppression activity of WT CREG [2].
  • The three potential glycosylation sites on CREG map to a confined patch opposite the dimer interface [2].
 

Biological context of CREG1

 

Anatomical context of CREG1

  • These studies suggest that secreted CREG protein participates in a signaling cascade important for differentiation of pluripotent stem cells such as those found in teratocarcinomas [6].
  • CREG mRNA is rapidly induced upon in vitro differentiation of both mouse embryonic stem cells and human NTERA-2 cells [6].
  • In absorption experiments with EBV-transformed cell lines, the POT-antigens removes preferentially anti-B7, Bw42 and Bw73 activity and to a lesser extent antibodies reactive with the B40 CREG-antigens [7].
  • CDC assay of human alloantisera specific for the HLA-B5 CREG against B*5103- or B*5101-transfected human B-cell line, Hmy2C1R (C1R), supported the belief that human alloantisera can discriminate B*5103 from B*5101 Ag [8].
  • Some array-identified gene products [integrin beta3, alpha-tubulin, regulatory telomere elongation protein (RAP1) and cellular repressor of EIA-stimulated genes (CREG protein)] were detected in human oocytes by immunofluorescence [9].
 

Associations of CREG1 with chemical compounds

  • CREG, a cellular repressor of E1A-stimulated genes, is a secreted glycoprotein that antagonizes cellular transformation by E1A and ras [1].
  • We show that constitutive expression of CREG in NTERA-2 cells enhances neuronal differentiation upon treatment with retinoic acid [6].
  • To test this hypothesis, confluent rat IECs (IEC-18) were cultured for 72 h with or without dexamethasone (DEX) and harvested for Western blot, immunocytochemistry, gene array and CREG immunoneutralization experiments [10].
  • Moreover, we found that 4D12 anti-B5, B35 CREG mAb cannot bind to B*5103 Ag on C1R cells or L cells although it binds to B*5101 Ag on both cells [8].
 

Regulatory relationships of CREG1

  • These studies reveal that CREG inhibits cell growth dependent on the M6P/IGF2R and suggest that interactions between CREG and a well-characterized tumor suppressor may contribute to regulation of proliferation and differentiation in multiple lineages [1].
 

Other interactions of CREG1

  • By analysing CREG activity in cells lacking M6P/IGF2R expression, we show that this receptor is required for CREG-induced growth inhibition [1].
  • This protein, termed CREG for cellular repressor of E1A-stimulated genes, shares limited sequence similarity with E1A and binds both the general transcription factor TBP and the tumor suppressor pRb in vitro [3].
 

Analytical, diagnostic and therapeutic context of CREG1

  • Northern blot analysis reveals that, although CREG mRNA is widely expressed in adult tissues, CREG mRNA is not significantly expressed in pluripotent mouse embryonic stem cells or NTERA-2 embryonal carcinoma cells [6].
  • IGFR-2 and CREG immunohistochemistry were also performed in archived ileal specimens from control and DEX-exposed newborn mice and extremely premature infants to investigate in vivo and clinical relevance [10].
  • Anti-HLA-A2 CREG antibodies were purified from seven individuals by affinity chromatography [11].
  • Cross-reactivity between antigens of the HLA-B7 cross-reactive group (B7 CREG) was investigated by the serological analysis of 60 "broad" cytotoxic HLA antisera produces by pregnancy alone, the HLA typing of the antiserum donors and the identification of their immunizing antigens [12].
  • Based on this analysis, there may be a significant potential advantage of prospective Class I CREG over A, B matching for first cadaver kidney transplantation [13].

References

  1. The secreted glycoprotein CREG inhibits cell growth dependent on the mannose-6-phosphate/insulin-like growth factor II receptor. Di Bacco, A., Gill, G. Oncogene (2003) [Pubmed]
  2. The crystal structure of CREG, a secreted glycoprotein involved in cellular growth and differentiation. Sacher, M., Di Bacco, A., Lunin, V.V., Ye, Z., Wagner, J., Gill, G., Cygler, M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. A cellular repressor of E1A-stimulated genes that inhibits activation by E2F. Veal, E., Eisenstein, M., Tseng, Z.H., Gill, G. Mol. Cell. Biol. (1998) [Pubmed]
  4. A novel inhibitory role for CREG-mediated signalling in cardiac hypertrophy? Dilley, R.J. J. Hypertens. (2004) [Pubmed]
  5. Analysis of risk factors for the development of late hepatic artery thrombosis: do CREG mismatches play a role? Neuhaus, P., Neumann, U. Liver Transpl. (2000) [Pubmed]
  6. The secreted glycoprotein CREG enhances differentiation of NTERA-2 human embryonal carcinoma cells. Veal, E., Groisman, R., Eisenstein, M., Gill, G. Oncogene (2000) [Pubmed]
  7. HLA-B POT: a new HLA-antigen within the B7-cross reactive group. Reekers, P., van der Beucken, M., Andrien, M., Beelen, J., Mueller-Eckhardt, G., Schreuder, G.M. Tissue Antigens (1986) [Pubmed]
  8. Effect of single amino acid substitution at residue 167 of HLA-B51 on binding of antibodies and recognition of T cells. Nakayama, S., Kawaguchi, G., Karaki, S., Nagao, T., Uchida, H., Kashiwase, K., Akaza, T., Nasuno, T., Takiguchi, M. Hum. Immunol. (1994) [Pubmed]
  9. Identification of genes expressed in primate primordial oocytes. Arraztoa, J.A., Zhou, J., Marcu, D., Cheng, C., Bonner, R., Chen, M., Xiang, C., Brownstein, M., Maisey, K., Imarai, M., Bondy, C. Hum. Reprod. (2005) [Pubmed]
  10. The cellular repressor of E1A-stimulated genes mediates glucocorticoid-induced loss of the type-2 IGF receptor in ileal epithelial cells. Gordon, P.V., Paxton, J.B., Fox, N.S. J. Endocrinol. (2005) [Pubmed]
  11. Epitope fine specificity of human anti-HLA-A2 antibodies. Identification of four epitopes including a haptenlike epitope on HLA-A2 at lysine 127. De Vito, L.D., Mason, B.P., Jankowska-Gan, E., Hogan, K.T., Guo, J.W., Lutz, C.T., Sollinger, H.W., Burlingham, W.J. Hum. Immunol. (1993) [Pubmed]
  12. A reanalysis of the HLA-B7 cross-reactive group. Darke, C. Tissue Antigens (1983) [Pubmed]
  13. CREG matching for first cadaveric kidney transplants (TNX) performed by SEOPF centers between October 1987 and September 1995. Southeastern Organ Procurement Foundation. Thompson, J.S., Thacker, L.R. Clinical transplantation. (1996) [Pubmed]
 
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