PT  - JOURNAL ARTICLE
AU  - Chang, Hao-Yen
AU  - Fan, Chi-Chen
AU  - Chu, Po-Chen
AU  - Hong, Bo-En
AU  - Lee, Hyeon Jeong
AU  - Chang, Mau-Sun
TI  - hPuf-A/KIAA0020 Modulates PARP-1 Cleavage upon Genotoxic Stress
AID  - 10.1158/0008-5472.CAN-10-1831
DP  - 2011 Feb 01
TA  - Cancer Research
PG  - 1126--1134
VI  - 71
IP  - 3
4099  - http://cancerres.aacrjournals.org/content/71/3/1126.short
4100  - http://cancerres.aacrjournals.org/content/71/3/1126.full
SO  - Cancer Res2011 Feb 01; 71
AB  - 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. Cancer Res; 71(3); 1126–34. ©2011 AACR.