Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins.
A two-hybrid protein interaction screen was used to isolate cDNAs encoding human proteins that can interact with human CDK2 in yeast. A new member of the retinoblastoma susceptibility gene family, Rbr-2 (Rb-related), was obtained. The sequence of the Rbr-2 protein shares approximately 50% identify with p107 and homology to Rb within the pocket domain. Several lines of evidence indicate that Rbr-2 is the adenovirus E1A-associated p130. Like Rb and p107, p130Rbr-2 can bind to viral oncoproteins, SV40 large T antigen, and adenovirus E1A through its pocket domain. Although p130Rbr-2 does not bind to CDK2 in vitro, it can interact with cyclins, with a clear preference for D-type cyclins. Because both CDK2 and p130Rbr-2 show affinity for cyclins, we suggest that p130Rbr-2 and CDK2 interacted through a yeast-derived cyclin bridge in the two-hybrid screen. The gene encoding p130Rbr-2 mapped to 16q13, a region of frequent genomic alteration in human tumors.
Hannon
G J
GJ
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
Demetrick
D
D
Beach
D
D
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000595:Amino Acid Sequence; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D001483:Base Sequence; D042846:CDC2-CDC28 Kinases; D002874:Chromosome Mapping; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130
D017500:Adenovirus E1A Proteins; D000952:Antigens, Polyomavirus Transforming; D016213:Cyclins; D010750:Phosphoproteins; D011506:Proteins; C493837:RBL2 protein, human; D050717:Retinoblastoma-Like Protein p130; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases