{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T15:28:44Z","timestamp":1770478124305,"version":"3.49.0"},"reference-count":55,"publisher":"Cold Spring Harbor Laboratory","issue":"15","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[1998,8,1]]},"abstract":"<jats:p>The retinoblastoma tumor suppressor protein, RB, is a negative regulator of cell proliferation. Growth inhibitory activity of RB is attenuated by phosphorylation. Mutation of a combination of phosphorylation sites leads to a constitutively active RB. In Rat-1 cells, the phosphorylation-site-mutated (PSM)-RB, but not wild-type RB, can inhibit S-phase entry. In PSM-RB-arrested G<jats:sub>1<\/jats:sub> cells, normal levels of cyclin E and cyclin E-associated kinase activity were detected, but the expression of cyclin A was inhibited. The ectopic expression of cyclin E restored cyclin A expression and drove the PSM-RB expressing cells into S phase. Interestingly, Rat-1 cells coexpressing cyclin E and PSM-RB could not complete DNA replication. Microinjection of cells that have passed through the G<jats:sub>1<\/jats:sub>restriction point with plasmids expressing PSM-RB also led to the inhibition of DNA synthesis. The S-phase inhibitory activity of PSM-RB could be attenuated by the coinjection of SV40 T-antigen, adenovirus E1A, or a high level of E2F-1 expression plasmids. However, the S-phase inhibitory activity of PSM-RB could not be overcome by the coinjection of cyclin E or cyclin A expression plasmids. These results reveal a novel role for RB in the inhibition of S-phase progression that is distinct from the inhibition of the G<jats:sub>1<\/jats:sub>\/S transition, and suggest that continued phosphorylation of RB beyond G<jats:sub>1<\/jats:sub>\/S is required for the completion of DNA replication.<\/jats:p>","DOI":"10.1101\/gad.12.15.2278","type":"journal-article","created":{"date-parts":[[2008,2,20]],"date-time":"2008-02-20T22:52:17Z","timestamp":1203547937000},"page":"2278-2292","source":"Crossref","is-referenced-by-count":181,"title":["Inhibition of DNA synthesis by RB: effects on G<sub>1<\/sub>\/S transition and S-phase\u2009progression"],"prefix":"10.1101","volume":"12","author":[{"given":"Erik S.","family":"Knudsen","sequence":"first","affiliation":[]},{"given":"Carolan","family":"Buckmaster","sequence":"additional","affiliation":[]},{"given":"Tung-Ti","family":"Chen","sequence":"additional","affiliation":[]},{"given":"James R.","family":"Feramisco","sequence":"additional","affiliation":[]},{"given":"Jean Y.J.","family":"Wang","sequence":"additional","affiliation":[]}],"member":"246","published-online":{"date-parts":[[1998,8,1]]},"reference":[{"key":"2021111418553113000_12.15.2278.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.17.7900"},{"key":"2021111418553113000_12.15.2278.2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.17.5322"},{"key":"2021111418553113000_12.15.2278.3","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1997.3776"},{"key":"2021111418553113000_12.15.2278.4","first-page":"103","article-title":"Cell cycle regulation by the retinoblastoma family of growth inhibitor proteins.","volume":"1287","author":"Beijersbergen","year":"1996","journal-title":"Biochim. 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