HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 4, 2368-2376, January 23, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/4/2368    most recent M304774200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Baek, K.-H. Articles by Choi, H.-K. Search for Related Content PubMed PubMed Citation Articles by Baek, K.-H. Articles by Choi, H.-K. Social Bookmarking                      What's this?

DUB-1A, a Novel Deubiquitinating Enzyme Subfamily Member, Is Polyubiquitinated and Cytokine-inducible in B-lymphocytes^*

Kwang-Hyun Baek¶, Myung-Sun Kim, Yong-Soo Kim, Ju-Mi Shin, and Hee-Kyung Choi

From the Cell and Gene Therapy Research Institute and the Graduate School of Life Science and Biotechnology, Pochon CHA University, CHA General Hospital, Seoul 135-081, Korea

Recently, we isolated the Dub-2A gene, which encodes a novel murine deubiquitinating enzyme subfamily member, from a bacterial artificial chromosome library clone by PCR amplification with degenerate PCR primers for the Dub-2 cDNA (Baek, K.-H., Mondoux, M. A., Jaster, R., Fire-Levin E., and D'Andrea, A. D. (2001) Blood 98, 636–642). In this study, we analyzed two more clones from the library to isolate genes encoding other deubiquitinating enzymes. Dub-1A, which encodes the shortest member of the DUB subfamily of deubiquitinating enzymes so far, has been identified in both clones and characterized. Sequence analysis showed that Dub-1A encodes a 468-amino acid protein that has a molecular mass of 51 kDa and that contains a putative catalytic domain (Cys, His, and Asp) conserved among DUB proteins. The amino acid sequence of DUB-1A is 84.5, 84.7, and 85.3% identical to those of DUB-1, DUB-2, and DUB-2A, respectively. Reverse transcription-PCR revealed that Dub-1A is expressed not only in B-lymphocytes in response to interleukin-3 stimulation, but also in T-lymphocytes, brain, heart, liver, lung, kidney, ovary, and spleen. This suggests that Dub-1A may play essential roles in each of these organs. In vivo and in vitro deubiquitinating enzyme assays showed that DUB-1A has functional deubiquitinating activity and that the 5'-flanking sequence of Dub-1A has a functional enhancer domain as shown in Dub-1 and Dub-2A. Interestingly, immunoblot analysis revealed that DUB-1A is polyubiquitinated, indicating that it is degraded through proteasome-mediated degradation. In the absence of JAK2, Dub-1A was expressed at a lower level. This suggests that DUB-1A functions downstream of JAK2 kinase in the interleukin-3 signaling pathway.

Received for publication, May 7, 2003 , and in revised form, October 6, 2003.

^* This work was supported by Grant M102KL010001-03K1201-02520 from the Stem Cell Research Center of the 21st Century Frontier Research Program supported by the Ministry of Science and Technology, Republic of Korea. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY257250.

^¶ To whom correspondence should be addressed: Cell and Gene Therapy Research Inst., Pochon CHA University, CHA General Hospital, 605 Yeoksam 1-Dong, Kangnam-Gu, Seoul 135-081, Korea. Tel.: 82-2-3468-3197; Fax: 82-2-3468-3264; E-mail: baek{at}cha.ac.kr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?