Abstract
We have previously isolated the hpttg proto-oncogene, which is expressed in normal tissues containing proliferating cells and in several kinds of tumors. In fact, expression of hPTTG correlates with cell proliferation in a cell cycle-dependent manner. Recently it was reported that PTTG is a vertebrate analog of the yeast securins Pds1 and Cut2, which are involved in sister chromatid separation. Here we show that hPTTG binds to Ku, the regulatory subunit of the DNA-dependent protein kinase (DNA-PK). hPTTG and Ku associate both in vitro and in vivo and the DNA-PK catalytic subunit phosphorylates hPTTG in vitro. Furthermore, DNA double-strand breaks prevent hPTTG-Ku association and disrupt the hPTTG-Ku complexes, indicating that genome damaging events, which result in the induction of pathways that activate DNA repair mechanisms and halt cell cycle progression, might inhibit hPTTG-Ku interaction in vivo. We propose that hPTTG might connect DNA damage-response pathways with sister chromatid separation, delaying the onset of mitosis while DNA repair occurs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Nuclear*
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COS Cells
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Cell Differentiation
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Cell-Free System / chemistry
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Cell-Free System / metabolism
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DNA Damage
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DNA Helicases*
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DNA-Activated Protein Kinase
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dimerization
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HL-60 Cells
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HeLa Cells
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Humans
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Jurkat Cells
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Ku Autoantigen
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phosphorylation
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Protein Binding
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Protein Subunits
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Proto-Oncogene Mas
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae Proteins*
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Securin
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Substrate Specificity
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Two-Hybrid System Techniques
Substances
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Antigens, Nuclear
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DNA-Binding Proteins
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MAS1 protein, human
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Neoplasm Proteins
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Nuclear Proteins
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Protein Subunits
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Proto-Oncogene Mas
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins
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Securin
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high affinity DNA-binding factor, S cerevisiae
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pituitary tumor-transforming protein 1, human
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DNA-Activated Protein Kinase
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PRKDC protein, human
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Protein Serine-Threonine Kinases
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DNA Helicases
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XRCC5 protein, human
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Xrcc6 protein, human
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Ku Autoantigen