Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity.

Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity. Research Abstract Details 

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Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity. Abstract Text:

Ralph G Meyer,Mirella L Meyer-Ficca,Clifford J Whatcott,Elaine L Jacobson,Myron K Jacobson,

Poly(ADP-ribose)glycohydrolase (PARG) is the major enzyme capable of rapidly hydrolyzing poly(ADP-ribose) (PAR) formed by the diverse members of the PARP enzyme family. This study presents an alternative splice mechanism by which two novel PARG protein isoforms of 60 kDa and 55 kDa are expressed from the human PARG gene, termed hPARG60 and hPARG55, respectively. Homologous forms were found in the mouse (mPARG63 and mPARG58) supporting the hypothesis that expression of small PARG isoforms is conserved among mammals. A PARG protein of approximately 60 kDa has been described for decades but with its genetic basis unknown, it was hypothesized to be a product of posttranslational cleavage of larger PARG isoforms. While this is not excluded entirely, isolation and expression of cDNA clones from different sources of RNA indicate that alternative splicing leads to expression of a catalytically active hPARG60 in multiple cell compartments. A second enzyme, hPARG55, that can be expressed through alternative translation initiation from hPARG60 transcripts is strictly targeted to the mitochondria. Functional studies of a mitochondrial targeting signal (MTS) in PARG exon IV suggest that hPARG60 may be capable of shuttling between nucleus and mitochondria, which would be in line with a proposed function of PAR in genotoxic stress-dependent, nuclear-mitochondrial crosstalk.

Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity. Publishing Authors By Initials

RG Meyer,ML Meyer-Ficca,CJ Whatcott,EL Jacobson,MK Jacobson,

For similar genetic processes: gene expression: transcription, genetic research abstracts see: genetic processes: gene expression: transcription, genetic research

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Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Experimental cell research

VOLUME: 313

Page Numbers: 2920-36

Journal Abbreviation: Exp. Cell Res.

ISSN: 0014-4827

DAY: 19

MONTH: 04

YEAR: 2007

Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 373226

Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity. Keywords Mesh Terms:

KEYWORDS: Transcription, Genetic

MESH TERMS: metabolism

Chemical & Substance for Abstract: Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity. Information

Substance Name: poly ADP-ribose glycohydrolase

Registry Number: EC 3.2.1.143

Grant and Affiliation Information for Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity.

AFFILIATION: Department of Animal Biology and Mari Lowe Center for Comparative Oncology, University of Pennsylvania, Kennett Square, PA 19348, USA. meyerg@vet.upenn.edu

Country: United States

AGENCY: United States NICHD

GRANT: HD048837

ACRONYM: HD

MEDLINETA: Exp Cell Res

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