title: Cell cycle regulated phosphorylation of the telomere-associated protein TIN2.
abstract: The protein TIN2 is a member of telomere-binding protein complex that serves to cap and protect mammalian chromosome ends. As a number of proteins in this complex are phosphorylated in a cell cycle-dependent manner, we investigated whether TIN2 is modified by phosphorylation as well. We performed phospho-proteomic analysis of human TIN2, and identified two phosphorylated residues, serines 295 and 330. We demonstrated that both these sites were phosphorylated during mitosis in human cells, as detected by Phos-tag reagent and phosphorylation-specific antibodies. Phosphorylation of serines 295 and 330 appeared to be mediated, at least in part, by the mitotic kinase RSK2. Specifically, phosphorylation of TIN2 at both these residues was increased upon expression of RSK2 and reduced by an inhibitor of the RSK family of kinases. Moreover, RSK2 phosphorylated TIN2 in vitro. The identification of these specifically timed post-translational events during the cell cycle suggests a potential mitotic regulation of TIN2 by phosphorylation.
authors: Department of Pharmacology and Cancer Biology, Department of Radiation Oncology, DUMC, Durham, North Carolina, United States of America.
authors: Shuqun
authors: S
authors: Yang
authors: Christopher M
authors: CM
authors: Counter
mesh_terms: D000595:Amino Acid Sequence; D045163:Antibodies, Phospho-Specific / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D008938:Mitosis / Q000187:drug effects; D008969:Molecular Sequence Data; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011621:Pteridines / Q000494:pharmacology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D045163:Antibodies, Phospho-Specific; C516541:BI D1870; D011621:Pteridines; C440868:TINF2 protein, human; D034501:Telomere-Binding Proteins; D010768:Phosphoserine; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; D015739:Nocodazole
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