Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 86 kDa immediate early IE2 protein of human cytomegalovirus (HCMV) can activate transcription of both viral and cellular genes and can repress transcription from its own promoter. Using two in vivo assays, we provide evidence of a functional interaction between IE2 and the retinoblastoma (RB) protein: IE2 alleviates RB-induced repression of a promoter bearing E2F binding sites and RB alleviates IE2-mediated repression of its own promoter. These functional effects are likely to be a result of a direct contact between IE2 and RB, which we can demonstrate both in vitro and in HCMV-infected cells. The interaction between IE2 and RB shows similar characteristics to the interaction between RB and E1A. First, binding to IE2 requires an intact RB pocket domain. Secondly, the binding is sensitive to the phosphorylation state of RB, because cyclin A-CDK-induced phosphorylation of RB diminishes IE2 binding. Thirdly, the IE2 domain required for RB binding is separate to the domains necessary for TBP and TFIIB binding. Our results demonstrate that large and small DNA viruses have a common interface with the host cell, namely the association with the RB tumour suppressor protein.
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PMID:Functional interaction between the HCMV IE2 transactivator and the retinoblastoma protein. 802 74

The retinoblastoma (RB) tumour suppressor protein is capable of repressing the activity of promoters containing DNA binding sites for the transcription factor E2F. Recently a protein which binds RB and possesses the DNA binding characteristics of E2F has been cloned. Here we show that the E2F activation domain is the target for RB-induced repression. RB can silence the 57 residue E2F activation domain but cannot effectively repress an E2F mutant which has reduced RB binding capacity. Extensive mutagenesis of E2F shows residues involved in RB binding are required for transcription activation. Mutations which affect both functions most dramatically lie within the minimal RB binding region. A further subset of sensitive residues lies within a new repeat motif E/DF XX L X P which flanks the minimum RB binding site. These data show that RB can mask E2F residues involved in the activation process, possibly by mimicking a component of the transcriptional machinery. Consistent with this model, we find that the TATA box binding protein TBP can bind to the E2F activation domain in vitro in a manner indistinguishable from that of RB.
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PMID:The retinoblastoma protein binds E2F residues required for activation in vivo and TBP binding in vitro. 825 52

The pocket domain of the retinoblastoma (Rb) tumour suppressor is central to Rb function, and is frequently inactivated by the binding of the human papilloma virus E7 oncoprotein in cervical cancer. The crystal structure of the Rb pocket bound to a nine-residue E7 peptide containing the LxCxE motif, shared by other Rb-binding viral and cellular proteins, shows that the LxCxE peptide binds a highly conserved groove on the B-box portion of the pocket; the A-box portion appears to be required for the stable folding of the B box. Also highly conserved is the extensive A-B interface, suggesting that it may be an additional protein-binding site. The A and B boxes each contain the cyclin-fold structural motif, with the LxCxE-binding site on the B-box cyclin fold being similar to a Cdk2-binding site of cyclin A and to a TBP-binding site of TFIIB.
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PMID:Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7. 949 40