Expression of RB C pocket fragments in HSF induces delayed cell cycle progression and sensitizes to apoptosis upon cellular stresses.
The retinoblastoma protein (RB) plays an important role in growth suppression through the formation of multiple protein complexes with its target proteins using A/B and C pockets. Even though the A/B and C pockets co-operate for growth suppression, the function of RB in growth arrest is inhibited by the coexpression of RB C fragments with full length RB in the absence of p53, which implies that C pocket fragments are likely to act as a dominant-negative inhibitor of RB function. In contrast, the loss of the RB functions in the presence of p53 triggers a cell cycle arrest or apoptosis by p53-dependent pathways. Thus, it still remains to be elucidated whether the expression of RB C pocket fragments in the presence of p53 induces delayed cell cycle progression and sensitizes cells to apoptosis through p53-dependent pathways. Our results show that the expression of RB C pocket fragments not only induces delayed cell cycle progression, which is mediated by the down-regulation of cyclin A, cyclin E, and E2F-1, but also sensitizes cells to apoptosis through p53-dependent pathways.
Chung
Junah
J
Department of Microbiology, School of Medicine, Keimyung University, Taegu, Republic of Korea.
Cho
Jae-We
JW
Baek
Won-Ki
WK
Suh
Seong-Il
SI
Kwon
Taeg Kyu
TK
Park
Jong-Wook
JW
Suh
Min-Ho
MH
D017209:Apoptosis / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D016193:G1 Phase / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000166:cytology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D010446:Peptide Fragments; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53