The Rb-related p130 protein controls telomere lengthening through an interaction with a Rad50-interacting protein, RINT-1.
The oncogenic process often leads to a loss of normal telomere length control, usually as a result of activation of telomerase. Nevertheless, there are also telomerase-independent events that involve a Rad50-dependent recombination mechanism to maintain telomere length. Previous work has implicated the Rb family of proteins in the control of telomere length, and we now demonstrate that the p130 member of the Rb family is critical for telomere length control. p130 interacts specifically with the RINT-1 protein, previously identified as a Rad50-interacting protein. We further show that RINT-1 is essential for telomere length control. We propose that p130, forming a complex with Rad50 through RINT-1, blocks telomerase-independent telomere lengthening in normal cells. Given previous work implicating E2F in the control of telomerase gene expression, these results thus point to complementary roles for the Rb/E2F pathway in the control of telomere length.
Kong
Ling-Jie
LJ
Duke Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina 27708, USA.
Meloni
Alison R
AR
Nevins
Joseph R
JR
D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D034741:RNA, Small Interfering / Q000494:pharmacology; D050717:Retinoblastoma-Like Protein p130 / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C422909:RINT1 protein, human; D034741:RNA, Small Interfering; D050717:Retinoblastoma-Like Protein p130; D019098:Telomerase