Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells.

Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells. Research Abstract Details 

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Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells. Abstract Text:

Wei Jin,William R Reiley,Andrew J Lee,Ato Wright,Xuefeng Wu,Minying Zhang,Shao-Cong Sun,

Deubiquitinating enzymes (DUB) form a family of cysteine proteases that digests ubiquitin chains and reverses the process of protein ubiquitination. Despite the identification of a large number of DUBs, their physiological functions remain poorly defined. Here we provide genetic evidence that CYLD, a recently identified DUB, plays a crucial role in regulating the peripheral development and activation of B cells. Disruption of the CYLD gene in mice results in B cell hyperplasia and lymphoid organ enlargement. The CYLD-deficient B cells display surface markers indicative of spontaneous activation and are hyperproliferative upon in vitro stimulation. When challenged with antigens, the CYLD(-/-) mice develop exacerbated lymphoid organ abnormalities and abnormal B cell responses. Although the loss of CYLD has only a minor effect on B cell development in bone marrow, this genetic deficiency disrupts the balance of peripheral B cell populations with a significant increase in marginal zone B cells. In keeping with these functional abnormalities, the CYLD(-/-) B cells exhibit constitutive activation of the transcription factor NF-kappaB due to spontaneous activation of IkappaB kinase beta and degradation of the NF-kappaB inhibitor IkappaBalpha. These findings demonstrate a critical role for CYLD in regulating the basal activity of NF-kappaB and maintaining the naive phenotype and proper activation of B cells.

Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells. Publishing Authors By Initials

W Jin,WR Reiley,AJ Lee,A Wright,X Wu,M Zhang,SC Sun,

For similar proteins: ubiquitins: ubiquitin research abstracts see: proteins: ubiquitins: ubiquitin research

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Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells. Journal Published:

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

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 15884-93

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 27

MONTH: 03

YEAR: 2007

Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells. Keywords Mesh Terms:

KEYWORDS: Ubiquitin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells. Information

Substance Name: Cysteine Endopeptidases

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells.

AFFILIATION: Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA94922

ACRONYM: CA

MEDLINETA: J Biol Chem

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