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Nucleic Acids Res ; 29(6): 1300-7, 2001 Mar 15.
Article in English | MEDLINE | ID: mdl-11238996

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.


Subject(s)
Antigens, Nuclear , DNA Helicases , DNA-Binding Proteins/metabolism , Neoplasm Proteins/metabolism , Nuclear Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Saccharomyces cerevisiae Proteins , Animals , COS Cells , Cell Differentiation , Cell-Free System/chemistry , Cell-Free System/metabolism , DNA Damage , DNA-Activated Protein Kinase , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , Dimerization , HL-60 Cells , HeLa Cells , Humans , Jurkat Cells , Ku Autoantigen , Neoplasm Proteins/genetics , Nuclear Proteins/chemistry , Nuclear Proteins/genetics , Phosphorylation , Protein Binding , Protein Serine-Threonine Kinases/genetics , Protein Subunits , Proto-Oncogene Mas , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Saccharomyces cerevisiae/genetics , Securin , Substrate Specificity , Two-Hybrid System Techniques
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