Studies conducted at Ordway Research Institute on retinoblastoma recently published
2007 NOV 19 -- Scientists discuss in 'p21(Waf1/Cip1/Sdi1) mediates retinoblastoma protein degradation' new findings in retinoblastoma. "Damage-induced G1 checkpoint in mammalian cells involves upregulation of p53, which activates transcription of p21(Waf1) (CDKN1A). Inhibition of cyclin-dependent kinase (CDK)2 and CDK4/6 by p21 leads to dephosphorylation and activation of Rb," scientists writing in the journal Oncogene report. "We now show that ectopic p21 expression in human HT1080 fibrosarcoma cells causes not only dephosphorylation but also depletion of Rb; this effect was p53-independent and susceptible to a proteasome inhibitor. CDK inhibitor p27 (CDKN1B) also caused Rb dephosphorylation and depletion, but another CDK inhibitor p16 (CDKN2A) induced only dephosphorylation but not depletion of Rb. Rb depletion was observed in both HT1080 and HCT116 colon carcinoma cells, where p21 was induced by DNA-damaging agents. Rb depletion after DNA damage did not occur in the absence of p21, and it was reduced when p21 induction was inhibited by p21-targeting short hairpin RNA or by a transdominant inhibitor of p53," wrote E.V. Broude and colleagues, Ordway Research Institute. The researchers concluded: "These results indicate that p21 both activates Rb through dephosphorylation and inactivates it through degradation, suggesting negative feedback regulation of damage-induced cell-cycle checkpoint arrest." Broude and colleagues published their study in Oncogene (p21(Waf1/Cip1/Sdi1) mediates retinoblastoma protein degradation. Oncogene, 2007;26(48):6954-8). Additional information can be obtained by contacting E.V. Broude, Cancer Center, Ordway Research Institute, Albany, NY 12208 USA.. The publisher of the journal Oncogene can be contacted at: Nature Publishing Group, Macmillan Building, 4 Crinan St., London N1 9XW, England. Keywords: United States, Albany, Oncology, Ophthalmology, Retinoblastoma. This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2007, Clinical Oncology Week via NewsRx.com.
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