Hyperphosphorylated p107 and p130 bind to T-antigen: identification of a critical regulatory sequence present in RB but not in p107/p130.
The retinoblastoma tumor suppressor RB and its related proteins, p107 and p130, are targets of several viral oncoproteins, including SV40 large T-antigen (T-Ag) and adenovirus E1A. T-Ag and E1A each contains an LXCXE-peptide motif through which binding to the conserved 'A/B pocket' present in RB, p107 and p130 is achieved. The LXCXE-binding activity of RB, we have previously shown, is inhibited by phosphorylation at Thr 821 and 826 in the C-terminal region of RB. Thr 821 and its surrounding sequence is unique to RB and not found in p107 or p130. Interestingly, hyperphosphorylation of p107 does not disrupt its ability to bind T-Ag or to inhibit the transactivating function of E1A. Insertion of a fourteen amino acid sequence of RB containing Thr 821 into p107 prevents binding of T-Ag and E1A to phosphorylated p107. These results show that the RB sequence surrounding Thr 821 plays a critical role in the regulation of the 'A/B pocket' function. In addition, these data indicate that the protein binding functions of RB and p107 are not equivalently regulated by phosphorylation.
Knudsen
E S
ES
Department of Biology and the Cancer Center, University of California, San Diego, La Jolla 92093-0322, USA.
Wang
J Y
JY
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins; D012045:Regulatory Sequences, Nucleic Acid; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D000957:Antigens, Viral, Tumor; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C493844:RBL1 protein, human; C493837:RBL2 protein, human; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130