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- Title
Induction of DNA synthesis and apoptosis by regulated inactivation of a temperature-sensitive retinoblastoma protein.
- Authors
Tiemann, Frank; Hinds, Philip W.
- Abstract
The retinoblastoma protein, pRb, controls entry into the S phase of the cell cycle and acts as a tumor suppressor in many tissues. Re-introduction of pRb into tumor cells lacking this protein results in growth arrest, due in part to transcriptional repression of genes required for S phase. Several studies suggest that pRb may also be involved in terminal cell cycle exit as a result of the instigation of senescence or differentiation programs. To understand better these multiple growth-inhibitory properties of pRb, a temperature-sensitive mutant of pRb has been produced. This tspRb induces G1 arrest and morphological changes efficiently at the permissive temperature of 32.5°C, but is weakly functional at 37°C. Consistent with this, tspRb is compromised in nuclear association and E2F regulation at the non-permissive temperature, but regains these properties at 32.5°C. Serial activation and inactivation of tspRb in SAOS-2 cells does not allow proliferation, but rather leads to apoptotic cell death. Transient activation of pRb may kill tumor cells by establishing a conflict between persistent proliferation-inhibitory signals and renewed deregulation of pRb targets such as E2F, and may thus be a more potent means of eliminating these cells than through simple re-introduction of the tumor suppressor gene.
- Subjects
DNA synthesis; RETINOBLASTOMA; TRANSCRIPTION factors; APOPTOSIS; CELL cycle; TUMOR suppressor genes
- Publication
EMBO Journal, 1998, Vol 17, Issue 4, p1040
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/17.4.1040