Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment

Zhang Y.; Chen L.-Y.; Han X.Xie W.Kim H.Yang D.Liu D.Songyang Z.

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Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment

机译：Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment

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Telomere maintenance is essential for organisms with linear chromosomes and is carried out by telomerase during cell cycle. The precise mechanism by which cell cycle controls telomeric access of telomerase and telomere elongation in mammals remains largely unknown. Previous work has established oligonucleotide/oligosaccharide binding (OB) fold-containing telomeric protein TPP1, formerly known as TINT1, PTOP, and PIP1, as a key factor that regulates telomerase recruitment and activity. However, the role of TPP1 in cell cycle-dependent telomerase recruitment is unclear. Here, we report that human TPP1 is phosphorylated at multiple sites during cell cycle progression and associates with higher telomerase activity at late S/G2/M. Phosphorylation of Ser111 (S111) within the TPP1 OB fold appears important for cell cycle-dependent telomerase recruitment. Structural analysis indicates that phosphorylated S111 resides in the telomerase-interacting domain within the TPP1OBfold. Mutations that disrupt S111 phosphorylation led to decreased telomerase activity in the TPP1 complex and telomere shortening. Our findings provide insight into the regulatory pathways and structural basis that control cell cycle-dependent telomerase recruitment and telomere elongation through phosphorylation of TPP1.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第14期|5457-5462|共6页
作者
Zhang Y.; Chen L.-Y.; Han X.Xie W.Kim H.Yang D.Liu D.Songyang Z.;
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作者单位

Key Laboratory of Gene Engineering, Sun Yat-Sen University, Baylor College of Medicine, Guangzhou 510275, China;

Verna and Marrs Mclean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Post-translational modification; Signal transduction; Telomere capping;

Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment

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