Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins

Genes Dev. 1993 Dec;7(12A):2378-91. doi: 10.1101/gad.7.12a.2378.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenovirus E1A Proteins / metabolism
  • Amino Acid Sequence
  • Antigens, Polyomavirus Transforming / metabolism
  • Base Sequence
  • CDC2-CDC28 Kinases*
  • Chromosome Mapping
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases*
  • Cyclins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Phosphoproteins*
  • Protein Binding
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases*
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / metabolism
  • Retinoblastoma-Like Protein p130

Substances

  • Adenovirus E1A Proteins
  • Antigens, Polyomavirus Transforming
  • Cyclins
  • Phosphoproteins
  • Proteins
  • RBL2 protein, human
  • Retinoblastoma-Like Protein p130
  • Protein Kinases
  • Protein Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases

Associated data

  • GENBANK/L11593
  • GENBANK/L11594
  • GENBANK/L16016
  • GENBANK/L24529
  • GENBANK/S56762
  • GENBANK/S56763
  • GENBANK/S66936
  • GENBANK/S67171
  • GENBANK/Z15047
  • GENBANK/Z15048