FEBS Letters
Volume 583, Issue 9 , Pages 1409-1414, 6 May 2009

HSP70 protects BCL2L12 and BCL2L12A from N-terminal ubiquitination-mediated proteasomal degradation

Edited by Noboru Mizushima

  • Junwu Yang

      Affiliations

    • Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Yi Hong

      Affiliations

    • Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Wenzong Wang

      Affiliations

    • Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Weibing Wu

      Affiliations

    • Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Yayun Chi

      Affiliations

    • Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Hongliang Zong

      Affiliations

    • Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Xiangfei Kong

      Affiliations

    • Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Yuanyan Wei

      Affiliations

    • Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Xiaojing Yun

      Affiliations

    • Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Chunming Cheng

      Affiliations

    • Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China
    • ,
  • Kangli Chen

      Affiliations

    • Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Jianxin Gu

      Affiliations

    • Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China
    • Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China
    • Corresponding Author InformationCorresponding author. Address: Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China. Fax: +86 21 64437403.

Received 9 March 2009; received in revised form 4 April 2009; accepted 7 April 2009. published online 17 April 2009.

Abstract 

BCL2L12 has been found to be associated with favorable prognosis in breast cancer patients while correlated with tumorigenesis of glioblastoma and colon cancer. Here, we report that BCL2L12 and its transcript variant BCL2L12A are degraded through ubiquitin-proteasome system (UPS). Interestingly, the ubiquitinations and degradations of BCL2L12 and BCL2L12A are independent of the internal lysine residues but the first N-terminal residues. In addition, HSP70 was identified to interact with BCL2L12 and BCL2L12A and protected them from ubiquitinations and degradations in mammalian cells. In summary, HSP70 protects BCL2L12 and BCL2L12A from N-terminal ubiquitination-mediated proteasomal degradation.

Structured summary

MINT-7026352, MINT-7026366: BCL2L12 (uniprotkb:Q9HB09-1) physically interacts (MI:0218) with Hsp70 (uniprotkb:P62988) by anti tag coimmunoprecipitation (MI:0007)

MINT-7026290: BCL2L12 (uniprotkb:Q9HB09-1) physically interacts (MI:0218) with ubiquitin (uniprotkb:P62988) by pull down (MI:0096)

MINT-7026326: Hsp70 (uniprotkb:P08107) physically interacts (MI:0218) with BCL2L12A (uniprotkb:Q9HB09-2) by anti bait coimmunoprecipitation (MI:0006)

MINT-7026338: BCL2L12 (uniprotkb:Q9HB09-1) physically interacts (MI:0218) with Hsp70 (uniprotkb:P08107) by anti tag coimmunoprecipitation (MI:0007)

MINT-7026304: BCL2L12A (uniprotkb:Q9HB09-2) physically interacts (MI:0218) with Hsp70 (uniprotkb:P08107) by anti tag coimmunoprecipitation (MI:0007)

Keywords: BCL2L12, Ubiquitination, HSP70

Abbreviations: MG132, z-Leu-Leu-Leu-CHO, GAPDH, glyseraldehyde-3-phosphate dehydrogenase, Ub, ubiquitin, CHX, cycloheximide, EGFP, enhanced green fluorescence protein

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PII: S0014-5793(09)00290-7

doi:10.1016/j.febslet.2009.04.011

FEBS Letters
Volume 583, Issue 9 , Pages 1409-1414, 6 May 2009

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