Loss of poly(ADP-ribose) polymerase-2 leads to rapid development of spontaneous T-cell lymphomas in p53-deficient mice

被引：50

作者：

Nicolas, L. ^{[1
,2
]}

Martinez, C. ^{[3
]}

Baro, C. ^{[4
]}

Rodriguez, M. ^{[4
]}

Baroja-Mazo, A. ^{[3
]}

Sole, F. ^{[4
]}

Flores, J. M. ^{[5
]}

Ampurdanes, C. ^{[1
]}

Dantzer, F. ^{[6
]}

Martin-Caballero, J. ^{[1
]}

Aparicio, P. ^{[2
]}

Yelamos, J. ^{[1
]}

机构：

[1] IMIM Hosp Mar, Barcelona Biomed Res Pk PRBB, Dept Immunol, Barcelona 08003, Spain

[2] Univ Murcia, Dept Biochem Mol Biol & Immunol, Sch Med, Murcia, Spain

[3] Univ Murcia, Dept Surg, CIBERehd, Univ Hosp Virgen de la Arrixaca, Murcia, Spain

[4] IMIM Hosp Mar, Barcelona Biomed Res Pk, Dept Pathol, Barcelona 08003, Spain

[5] Univ Complutense, Dept Anim Surg & Med, Sch Vet, E-28040 Madrid, Spain

[6] ESBS, IREBS FRE3211, Strasbourg, France

来源：

ONCOGENE | 2010年 / 29卷 / 19期

关键词：

Parp-2; p53; tumour development; thymocytes; V(D)J recombination; double-strand breaks; DOUBLE-STRAND BREAKS; DNA-DAMAGE; CHROMOSOMAL-ABERRATIONS; GENOMIC STABILITY; REPAIR; P53; RECOMBINATION; TUMORIGENESIS; INHIBITION; DEFICIENCY;

D O I：

10.1038/onc.2010.11

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Poly(ADP-ribose) polymerase-2 (Parp-2) belongs to a family of enzymes that catalyse poly(ADP-ribosyl) ation of proteins. Parp-2 deficiency in mice (Parp-2(-/-)) results in reduced thymic cellularity associated with increased apoptosis in thymocytes, defining Parp-2 as an important mediator of T-cell survival during thymopoiesis. To determine whether there is a link between Parp-2 and the p53 DNA-damage-dependent apoptotic response, we have generated Parp-2/p53-double-null mutant mice. We found that p53(-/-) backgrounds completely restored the survival and development of Parp-2(-/-) thymocytes. However, Parp-2-deficient thymocytes accumulated high levels of DNA double-strand breaks (DSB), independently of the p53 status, in line with a function of Parp-2 as a caretaker promoting genomic stability during thymocytes development. Although Parp-2(-/-) mice do not have spontaneous tumours, Parp-2 deficiency accelerated spontaneous tumour development in p53-null mice, mainly T-cell lymphomas. These data suggest a synergistic interaction between Parp-2 and p53 in tumour suppression through the role of Parp-2 in DNA-damage response and genome integrity surveillance, and point to the potential importance of examining human tumours for the status of both genes. Oncogene (2010) 29, 2877-2883; doi: 10.1038/onc.2010.11; published online 15 February 2010

引用

页码：2877 / 2883

页数：7

共 39 条

[1]

Peroxisome proliferator-activated receptor (PPAR)-2 controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the retinoid x receptor/PPARγ heterodimer [J].