Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase.
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.
Romero
F
F
Departamento de Microbiología, Facultad de Biología, Universidad de Sevilla, Apdo. 1095, 41080-Sevilla, Spain. frport@cica.es
Multon
M C
MC
Ramos-Morales
F
F
Domínguez
A
A
Bernal
J A
JA
Pintor-Toro
J A
JA
Tortolero
M
M
D000818:Animals; D034961:Antigens, Nuclear; D019556:COS Cells; D002454:Cell Differentiation; D002474:Cell-Free System / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D000072200:Ku Autoantigen; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits; D000090063:Proto-Oncogene Mas; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D000090063:Proto-Oncogene Mas; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; C081647:high affinity DNA-binding factor, S cerevisiae; C578002:pituitary tumor-transforming protein 1, human; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen