Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-1-26
pubmed:abstractText
Poly(ADP-ribose) polymerase 1 (PARP1) modifies a variety of nuclear proteins by poly(ADP-ribosyl)ation, and plays diverse roles in molecular and cellular processes. A common PARP1 single nucleotide polymorphism (SNP) at codon 762, resulting in the substitution of alanine (Ala) for valine (Val) in the catalytic domain has been implicated in susceptibility to cancer. To characterize the functional effect of this polymorphism on PARP1, we performed in vitro enzymatic analysis on PARP1-Ala762 and PARP1-Val762. We found that PARP1-Ala762 displayed 57.2% of the activity of PARP1-Val762 for auto-poly(ADP-ribosyl)ation and 61.9% of the activity of PARP1-Val762 for trans-poly(ADP-ribosyl)ation of histone H1. The kinetic characterization revealed that the K(m) of PARP1-Ala762 was increased to a 1.2-fold of the K(m) of PARP1-Val762 for trans-poly(ADP-ribosyl)ation. Thus, the PARP1 Val762Ala polymorphism reduces the enzymatic activity of PARP1 by increasing K(m). This finding suggests that different levels of poly(ADP-ribosyl)ation by PARP1 might aid in understanding the cancer risk of carriers of the PARP1 Val762Ala polymorphism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
354
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
122-6
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
PARP1 Val762Ala polymorphism reduces enzymatic activity.
pubmed:affiliation
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), 5 Dong Dan San Tiao, 100005 Beijing, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't