Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis.

Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis. Research Abstract Details 

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Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis. Abstract Text:

Toshiki Itoh,Sachiyo Iwashita,Michael B Cohen,David K Meyerholz,Stuart Linn,

Damage-specific DNA-binding (DDB) protein heterodimer has been extensively studied in the context of nucleotide excision repair. However, the smaller subunit, DDB2, is also implicated in tumor suppressor p53-mediated processes, although the precise details of the DDB2 - p53 interactions are unknown. Here, we report that Ddb2(-/-) and Ddb2(+/-) mice have shortened lifespans and increased frequency and spectrum of spontaneous tumors. Notably, Ddb2 deficiency enhances lung and mammary adenocarcinomas. Ddb2(-/-) mice are smaller than normal. Whereas weights of kidneys and livers are reduced proportionately, spleens from Ddb2(-/-) mice gradually enlarge with age due to lymphoid proliferation. Ddb2(-/-) mice also have larger testes, and the testicular germ cells show significantly decreased spontaneous apoptosis. These changes parallel reduced levels of p53 and its serine 15 phosphorylation in testicular germ cells. Since tumors that appeared in heterozygous Ddb2(+/-) mice conserve the wild-type Ddb2 allele, Ddb2 RNA expression and Ddb2 exon sequence, Ddb2 heterozygosity can facilitate tumor development as a haploinsufficient tumor suppressor. These results demonstrate that in whole animals as in cultured cells Ddb2 can regulate apoptosis and tumor incidence.

Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis. Publishing Authors By Initials

T Itoh,S Iwashita,MB Cohen,DK Meyerholz,S Linn,

For similar urogenital system: genitalia: genitalia, male: testis research abstracts see: urogenital system: genitalia: genitalia, male: testis research

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Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Human molecular genetics

VOLUME: 16

Page Numbers: 1578-86

Journal Abbreviation: Hum. Mol. Genet.

ISSN: 0964-6906

DAY: 27

MONTH: 04

YEAR: 2007

Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis. Information

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LANGUAGE: eng

NlmUniqueID: 9208958

Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis. Keywords Mesh Terms:

KEYWORDS: Testis

MESH TERMS: metabolism

Chemical & Substance for Abstract: Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis. Information

Substance Name: Serine

Registry Number: 56-45-1

Grant and Affiliation Information for Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis.

AFFILIATION: Department of Pathology, The University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA. toshiki-ito@uiowa.edu

Country: England

AGENCY: United States NIGMS

GRANT: GM050424

ACRONYM: GM

MEDLINETA: Hum Mol Genet

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