Human hPuf-A/KIAA0020 was first identified as a new minor histocompatibility antigen in 2001. Its zebrafish ortholog 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 an hPuf-A-interacting protein. hPuf-A specifically interacts with the catalytic domain of PARP-1 and inhibits poly(ADPribosyl)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.
Human hPuf-A/KIAA0020 was first identified as a new minor histocompatibility antigen in 2001. Its zebrafish ortholog 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 an hPuf-A-interacting protein. hPuf-A specifically interacts with the catalytic domain of PARP-1 and inhibits poly(ADPribosyl)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.
Positions Held
- 2012 – present Associate Professor, Inst. Biochem. Sciences, National Taiwan University
- 2008 – present Joint Appointment Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica
- 2008 – 2012 Assistant Professor, Inst. Biochem. Sciences, National Taiwan University
- 2005 – 2008 Investigator, Dept. of Medical Research, Mackay Memorial Hospita
- 1999 – 2004 Associate Investigator, Dept. of Medical Research, Mackay Memorial Hospital
- 1997 – 1999 Postdoc fellow, Dana-Farber Cancer Institute, Harvard Medical School
Degrees
- 1993 – 1997 Ph.D., Department of Zoology, National Taiwan University
- 1992 – 1993 M.S., Department of Zoology, National Taiwan University
- 1985 – 1989 B.S., Department of Zoology, National Taiwan University
- Lin HW, Lee JY, Chou NL, Shih TW, (Chang MS) (2021-08) PloS one 16(8), e0256282 “Phosphorylation of PUF-A/PUM3 on Y259 modulates PUF-A stability and cell proliferation.”
- Lee JY, Fan CC, Chou NL, Lin HW, (Chang MS) (2020-07) PloS one 15(7), e0236876 “PHRF1 promotes migration and invasion by modulating ZEB1 expression.”
- Shih TW, Lee LJ, Chang HC, Lin HW, (Chang MS) (2020-07) Scientific reports 10(1), 10857 “An important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-beta signaling.”
- Fan JJ, Hsu WH, Lee KH, Chen KC, Lin CW, Lee YA, Ko TP, Lee LT, Lee MT, (Chang MS), Cheng CH (2019-11) Antioxidants 8(11), E557 “Dietary Flavonoids Luteolin and Quercetin Inhibit Migration and Invasion of Squamous Carcinoma through Reduction of Src/Stat3/S100A7 Signaling.”
- Lee JY, Lee LJ, Fan CC, Chang HC, Shih HA, Min MY, (Chang MS) (2017-04) Scientific Reports 7, 45646 “Important roles of Vilse in dendritic architecture and synaptic plasticity.”
- Su WP, Hsu SH, Chia LC, Lin JY, Chang SB, Jiang ZD, Lin YJ, Shih MY, Chen YC, Chang MS, Yang WB, Hung JJ, Hung PC, Wu WS, Myung K, Liaw H (2016-01) Genetics 202(1), 77-92 “Combined Interactions of Plant Homeodomain and Chromodomain Regulate NuA4 Activity at DNA Double-Strand Breaks.”
- Chang CF, Chu PC, Wu PY, Yu MY, Lee JY, Tsai MD, (Chang MS) (2015-04) Cell death & disease 6, e1716 “PHRF1 promotes genome integrity by modulating non-homologous end-joining.”
- Cheng CH, Chou CM, Chu CY, Chen GD, Lien HW, Hwang PP, (Chang MS), Huang CJ (2014) Fish & shellfish immunology 38(1), 230-43 “Differential regulation of Tetraodon nigroviridis Mx gene promoter activity by constitutively-active forms of STAT1, STAT2, and IRF9.”
- Zhong W, Zhou Y, Li J, Mysore R, Luo W, Li S, (Chang MS), Olkkonen VM, Yan D (2014) Experimental cell research 322(2), 227-235 “OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle.”
- Fan CC, Lee LY, Yu MY, Tzen CY, Chou C, (Chang MS) (2013-10) TUMOR BIOLOGY 34(5), 2557-2564 “Upregulated hPuf-A promotes breast cancer tumorigenesis.”
- Chen YL, Jiang YW, Su YL, Lee SC, (Chang MS), Chang CJ (2013-04) Molecular biology reports 40(4), 2867-2877 “Transcriptional regulation of tristetraprolin by NF-kappaB signaling in LPS-stimulated macrophages.”
- Chen CH, Chu PC, Lee L, Lien HW, Lin TL, Fan CC, Chi P, Huang CJ, (Chang MS) (2012) PloS one 7(3), e33538 “Disruption of Murine mp29/Syf2/Ntc31 Gene Results in Embryonic Lethality with Aberrant Checkpoint Response.”
- Yeh PA, Yang WH, Chiang PY, Wang SC, (Chang MS), Chang CJ (2012) International journal of biological sciences 8(5), 606-19 “Drosophila eyes absent is a novel mRNA target of the tristetraprolin (TTP) protein DTIS11.”
- Chang HY, Fan CC, Chu PC, Hong BE, Lee HJ, (Chang MS) (2011-02) Cancer research 71(3), 1126-34 “hPuf-A/KIAA0020 Modulates PARP-1 Cleavage upon Genotoxic Stress.”
- Chu PC, Wang TY, Lu YT, Chou CK, Yang YC, Chang MS (2009-10) Carcinogenesis 30(10), 1710-1716 “Involvement of p29 in DNA damage responses and Fanconi anemia pathway.”
- Cheng TS, Hsiao YL, Lin CC, Yu CT, Hsu CM, Chang MS, Lee CI, Huang CY, Howng SL, Hong YR (2008) The Journal of biological chemistry 283(4), 2454-64 “Glycogen synthase kinase 3beta interacts with and phosphorylates the spindle-associated protein astrin.”
- Cheng TS, Hsiao YL, Lin CC, Hsu CM, Chang MS, Lee CI, Yu RC, Huang CY, Howng SL, Hong YR (2007) Experimental cell research 313(8), 1710-21 “hNinein is required for targeting spindle-associated protein Astrin to the centrosome during the S and G2 phases.”
- Twu YC, Chen CP, Hsieh CY, Tzeng CH, Sun CF, Wang SF, Chang MS, Yu LC. (2007) Blood 110(13), 4526-4534 “I branching formation in erythroid differentiation is regulated by transcription factor C/EBPα”
- Ho HT, Chang MS, Wei TY, Hsieh WS, Hung CC, Yang HM, Lu YT (2006) Chest 129(1), 95-101 “Colonization of severe acute respiratory syndrome-associated coronavirus among health-care workers screened by nasopharyngeal swab.”
- Chan WE, Chuang CK, Yeh SH, Chang MS, Chen SS (2006) Journal of virology 80(7), 3225-37 “Functional characterization of heptad repeat 1 and 2 mutants of the spike protein of severe acute respiratory syndrome coronavirus.”
- Yang YC, Hsu YT, Wu CC, Chen HT, Chang MS (2006) Biochemical and biophysical research communications 343(2), 428-34 “Silencing of astrin induces the p53-dependent apoptosis by suppression of HPV18 E6 expression and sensitizes cells to paclitaxel treatment in HeLa cells.”
- Chu PC, Yang YC, Lu YT, Chen HT, Yu LC, Chang MS (2006) Cancer research 66(17), 8484-91 “Silencing of p29 affects DNA damage responses with UV irradiation.”
- Chang MS, Yang YC, Kuo YC, Kuo YH, Chang C, Chen CM, Lee TH (2005) Journal of natural products 68(1), 11-3 “Furocoumarin glycosides from the leaves of Ficus ruficaulis Merr. var. antaoensis.”