Functional analysis of pRb2/p130 interaction with cyclins.
The retinoblastoma (Rb) family consists of the tumor suppressor pRb and related proteins p107 and pRb2/p130. Ectopic expression of pRb and p107 results in a growth arrest of sensitive cells in the G1 phase of the cell cycle. We demonstrated here that the growth-suppressive properties of pRb2/p130 were also specific for the G1 phase. The A-, E-, and D-type cyclins as well as transcription factor E2F1 and the E1A viral oncoprotein were able to rescue the pRb2/p130-mediated G1 growth arrest in SAOS-2 cells. The rescue with cyclins A and E correlated with their physical interaction with pRb2/p130, which surprisingly has been found to occur over all phases of the cell cycle. The phosphorylation status as well as the kinase activity associated with pRb2/p130 dramatically increased near the G1-S-phase transition. This suggests that, like the other Rb family members, pRb and p107, the phosphorylation of pRb2/p130 is controlled by the cell cycle machinery and that pRb2/p130 may indeed be another key G1-S-phase regulator.
Claudio
P P
PP
Department of Microbiology-Immunology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
De Luca
A
A
Howard
C M
CM
Baldi
A
A
Firpo
E J
EJ
Koff
A
A
Paggi
M G
MG
Giordano
A
A
D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000235:genetics*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase / Q000235:genetics; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011506:Proteins; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D016196:S Phase / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D016213:Cyclins; D010750:Phosphoproteins; D011506:Proteins; C493837:RBL2 protein, human; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases