Functional interaction between the HCMV IE2 transactivator and the retinoblastoma protein.
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.
Hagemeier
C
C
Wellcome/CRC Institute, Cambridge, UK.
Caswell
R
R
Hayhurst
G
G
Sinclair
J
J
Kouzarides
T
T
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D002478:Cells, Cultured; D016213:Cyclins / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics*; D005786:Gene Expression Regulation; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008562:Membrane Glycoproteins; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014759:Viral Envelope Proteins; D014764:Viral Proteins
D017500:Adenovirus E1A Proteins; D016213:Cyclins; C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D016160:Retinoblastoma Protein; D015534:Trans-Activators; C077406:UL115 protein, Human herpesvirus 5; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; C439068:glycoprotein O, cytomegalovirus; D011494:Protein Kinases