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Journal of Biochemistry Advance Access originally published online on October 9, 2008
Journal of Biochemistry 2009 145(1):1-12; doi:10.1093/jb/mvn135
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© The Authors 2008. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved

PPM1D430, a Novel Alternative Splicing Variant of the Human PPM1D, can Dephosphorylate p53 and Exhibits Specific Tissue Expression

Yoshiro Chuman, Wataru Kurihashi, Yohei Mizukami, Takehiro Nashimoto, Hiroaki Yagi and Kazuyasu Sakaguchi*

Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, 060-0810, Japan

*To whom correspondence should be addressed. Tel: +81-11-706-2698, Fax: +81-11-706-4683, E-mail: kazuyasu{at}sci.hokudai.ac.jp

Received July 25, 2008; Accepted September 25, 2008


  Abstract

PPM1D is a PPM1 type protein phosphatase and is induced in response to DNA damage. PPM1D-deficient mice show defects in spermatogenesis and lymphoid cell functions but the mechanisms underlying these phenotypes remain unknown. In our current study, we identify and characterize an alternative splicing variant (denoted PPM1D430) of human PPM1D at both the mRNA and protein level. PPM1D430 comprises the common 420 residues of the known PPM1D protein (PPM1D605) and contains a stretch of PPM1D430-specific 10 amino acids. Semi-quantitative reverse transcription–polymerase chain reaction (RT–PCR) analysis revealed that PPM1D430 mRNA is also induced in response to the genotoxic stress in a p53-dependent manner. In vitro phosphatase analysis and PPM1D430-specific RNA interference analysis further indicated that PPM1D430 can dephosphorylate Ser15 of human p53 both in vitro and in vivo. On the other hand, expression profiling of this gene by RT–PCR analysis of a human tissue cDNA panel revealed that PPM1D430 is expressed exclusively in testes and in leucocytes whereas PPM1D605 is ubiquitous. In addition, PPM1D430 shows a different subcellular localization pattern and protein stability when compared with PPM1D605 under some conditions. Our current findings thus suggest that PPM1D430 may exert specific functions in immune response and/or spermatogenesis.

Key Words: alternative splicing variant, p53, phosphatase, PPM1D, tissue-specific expression

Abbreviations: ADR, adriamycin; ATM, ataxia-telangiectasia-mutated; EGFP, enhanced green fluorescent protein; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HRG, Heregulin; hPPAR {gamma}, human peroxisome proliferator-activated receptor {gamma}; IR, ionizing radiation; MDM2, mouse double minute 2; NLS, nuclear localization signal; NMD, nonsense-mediated decay; PP2C, Protein Phosphatase type 2C; PPM, Mg2+- or Mn2+-dependent protein phosphatase; PPM1D, Protein Phosphatase Magnesium-dependent 1, delta; S(P), phosphorylated Serine; UNG2, uracil DNA glycosylase 2


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