The PCNA-associated factor KIAA0101/p15(PAF) binds the potential tumor suppressor product p33ING1b.
The KIAA0101/p15(PAF)/OEATC-1 protein was initially isolated in a yeast two-hybrid screen for proliferating cell nuclear antigen (PCNA) binding partners, and was shown to bind PCNA competitively with the cell cycle regulator p21(WAF). PCNA is involved in DNA replication and damage repair. Using polyclonal antisera raised against a p15(PAF) fusion protein, we have shown that in a range of mammalian tumor and non-tumor cell lines the endogenous p15(PAF) protein localises to the nucleus and the mitochondria. Under normal conditions no co-localisation with PCNA could be detected, however following exposure to UV it was possible to co-immunoprecipitate p15(PAF) and PCNA from a number of cell lines, suggesting a UV-enhanced association of the two proteins. Overexpression of p15(PAF) in mammalian cells was also found to protect cells from UV-induced cell death. Based on similarities between the behaviour of p15(PAF) and the potential tumor suppressor product p33ING1b, we have further shown that these two proteins interact in the same complex in cell cultures. This suggests that p15(PAF) forms part of a larger protein complex potentially involved in the regulation of DNA repair, apoptosis and cell cycle progression.
Simpson
Fiona
F
Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
Lammerts van Bueren
Kelly
K
Butterfield
Natalie
N
Bennetts
Jennifer S
JS
Bowles
Josephine
J
Adolphe
Christelle
C
Simms
Lisa A
LA
Young
Joanne
J
Walsh
Michael D
MD
Leggett
Barbara
B
Fowles
Lindsay F
LF
Wicking
Carol
C
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D016923:Cell Death / Q000528:radiation effects*; D002467:Cell Nucleus / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D047468:Immunoprecipitation; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014466:Ultraviolet Rays
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501503:ING1 protein, human; D007074:Immunoglobulin G; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C425208:PCLAF protein, human; D018809:Proliferating Cell Nuclear Antigen; D025521:Tumor Suppressor Proteins; D012313:RNA; D004247:DNA