A Unique Domain of pRb2/p130 Acts as an Inhibitor of Cdk2 Kinase Activity

The Cdk2 kinase has long been known to be involved in the progression of mammalian cells past the G1 phase restriction point and through DNA replication in the cell cycle. The Rb family of proteins, consisting of pRb, p107, and pRb2/p130, has also been shown to monitor progression of G1 phase, mostl...

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Bibliographic Details
Published in:The Journal of biological chemistry 1997-08, Vol.272 (34), p.20971-20974
Main Authors: De Luca, Antonio, MacLachlan, Timothy K., Bagella, Luigi, Dean, Charity, Howard, Candace M., Claudio, Pier Paolo, Baldi, Alfonso, Khalili, Kamel, Giordano, Antonio
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Carrier Proteins
CDC2-CDC28 Kinases
Cell Cycle
Cell Cycle Proteins
Cell Differentiation
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinases - antagonists & inhibitors
DNA-Binding Proteins
E2F Transcription Factors
Mice
Nuclear Proteins - metabolism
Phosphoproteins - chemistry
Protein Binding
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Proteins
Recombinant Proteins
Retinoblastoma Protein - metabolism
Retinoblastoma-Binding Protein 1
Retinoblastoma-Like Protein p107
Retinoblastoma-Like Protein p130
Transcription Factor DP1
Transcription Factors - metabolism
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Summary:The Cdk2 kinase has long been known to be involved in the progression of mammalian cells past the G1 phase restriction point and through DNA replication in the cell cycle. The Rb family of proteins, consisting of pRb, p107, and pRb2/p130, has also been shown to monitor progression of G1 phase, mostly through their interaction with E2F family members. p107 is able to inhibit Cdk2 kinase activity through this interaction via a p21-related domain present in the C terminus of the protein. We show here that pRb2/p130 also possesses this activity, but through a separate domain. Moreover, we correlate the increased expression of pRb2/p130 during various cellular processes with the decreased kinase activity of Cdk2. We hypothesize that pRb2/p130 may act not only to bind and modify E2F activity, but also to inhibit Cdk2 kinase activity in concert with p21 in a manner different from p107.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.272.34.20971