Physical interaction of the retinoblastoma protein with human D cyclins.
The retinoblastoma protein (pRb) functions as a regulator of cell proliferation and in turn is regulated by cyclin-dependent kinases. Cyclins D1 and D3 can form complexes with pRb that resemble those formed by several viral oncoproteins and are disrupted by the adenovirus E1A oncoprotein and derived peptides. These cyclins contain a sequence motif similar to the pRb-binding conserved region II motif of the viral oncoproteins. Alteration of this motif in cyclin D1 prevents formation of cyclin D1-pRb complexes while enhancing the biological activity of cyclin D1 assayed in vivo. We conclude that cyclins D1 and D3 interact with pRb in a fashion distinct from cyclins A and E, which can induce pRb hyperphosphorylation, and that cyclin D1 activity may be regulated by its association with pRb.
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
S F
SF
Dowdy
P W
PW
Hinds
K
K
Louie
S I
SI
Reed
A
A
Arnold
R A
RA
Weinberg
D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle; D002874:Chromosome Mapping; D019938:Cyclin D1; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016161:Genes, Retinoblastoma; D006801:Humans; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D012516:Osteosarcoma; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
C080336:CCND2 protein, human; C534696:CCND3 protein, human; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins; D015513:Oncogene Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1