hPuf-A/KIAA0020 Modulates PARP-1 Cleavage upon Genotoxic Stress
Resource
CANCER RESEARCH, 71(3), 1126-1134
Journal
Cancer Research
Journal Volume
71
Journal Issue
3
Pages
1126-1134
Date Issued
2011
Date
2011
Author(s)
Abstract
Human hPuf-A/KIAA0020 was first identified as a new minor histocompatibility antigen in 2001. Its zebrafish orthologue contains six Pumilio-homology RNA-binding domains and has been shown to participate in the development of eyes and primordial germ cells, but the cellular function of hPuf-A remains unclear. In this report, we showed that hPuf-A predominantly localized in the nucleoli with minor punctate signals in the nucleoplasm. The nucleolar localization of hPuf-A would redistribute to the nucleoplasm after the treatment of RNA polymerase inhibitors (actinomycin D and 5,6- dichlorobenzimidazole riboside) and topoisomerase inhibitors [camptothecin (CPT) and etoposide]. Interestingly, knockdown of hPuf-A sensitized cells to CPT and UV treatment and cells constitutively overexpressing hPuf-A became more resistant to genotoxic exposure. Affinity gel pull-down coupled with mass spectrometric analysis identified PARP-1 as one of the hPuf-A interacting proteins. hPuf-A specifically interacts with the catalytic domain of PARP-1 and inhibits poly(ADP-ribosyl) ation of PARP-1 in vitro. Depletion of hPuf-A increased the cleaved PARP-1 and overexpression of hPuf-A lessened PARP-1 cleavage when cells were exposed to CPT and UV light. Collectively, hPuf-A may regulate cellular response to genotoxic stress by inhibiting PARP-1 activity and thus preventing PARP-1 degradation by caspase-3. ©2011 AACR.
Other Subjects
5,6 dichlorobenzimidazole riboside; camptothecin; caspase 3; dactinomycin; etoposide; hPuf A protein; minor histocompatibility antigen; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; nuclear protein; poly(adenosine diphosphate ribose); unclassified drug; adenosine diphosphate ribosylation; article; cell nucleus; cellular distribution; cellular stress response; chemosensitization; controlled study; female; gene overexpression; genotoxicity; human; human cell; in vitro study; intracellular signaling; priority journal; protein cleavage; protein degradation; protein domain; protein function; protein localization; protein protein interaction; radiosensitization; ultraviolet radiation; Amino Acid Sequence; Caspase 3; Cell Line, Tumor; Cell Nucleolus; DNA Damage; Gene Knockdown Techniques; HEK293 Cells; Hela Cells; Humans; Molecular Sequence Data; Poly(ADP-ribose) Polymerases; RNA, Small Interfering; RNA-Binding Proteins; Sequence Alignment; Transfection
Type
journal article
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