FEBS Letters
Volume 583, Issue 4 , Pages 648-654, 18 February 2009

Degradation of transglutaminase 2 by calcium-mediated ubiquitination responding to high oxidative stress

Edited by Vladimir Skulachev

  • Eui Man Jeong

      Affiliations

    • Department of Biochemistry and Molecular Biology/Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, 28 Yongon Dong, Chongno Gu, Seoul 110-799, Republic of Korea
    • These authors contribute equally.
  • ,
  • Chai-Wan Kim

      Affiliations

    • Department of Biochemistry and Molecular Biology/Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, 28 Yongon Dong, Chongno Gu, Seoul 110-799, Republic of Korea
    • These authors contribute equally.
  • ,
  • Sung-Yup Cho

      Affiliations

    • Department of Biochemistry and Molecular Biology/Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, 28 Yongon Dong, Chongno Gu, Seoul 110-799, Republic of Korea
  • ,
  • Gi-Yong Jang

      Affiliations

    • Department of Biochemistry and Molecular Biology/Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, 28 Yongon Dong, Chongno Gu, Seoul 110-799, Republic of Korea
  • ,
  • Dong-Myung Shin

      Affiliations

    • Department of Biochemistry and Molecular Biology/Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, 28 Yongon Dong, Chongno Gu, Seoul 110-799, Republic of Korea
  • ,
  • Ju-Hong Jeon

      Affiliations

    • Department of Physiology and Biophysics, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
  • ,
  • In-Gyu Kim

      Affiliations

    • Department of Biochemistry and Molecular Biology/Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, 28 Yongon Dong, Chongno Gu, Seoul 110-799, Republic of Korea
    • Corresponding Author InformationCorresponding author. Fax: +82 2 744 4534.

Received 28 November 2008; received in revised form 7 January 2009; accepted 19 January 2009. published online 28 January 2009.

Abstract 

Transglutaminase 2 (TG2) is a calcium-dependent enzyme that catalyzes the transamidation reaction. There is conflicting evidence on the role of TG2 in apoptosis. In this report, we show that TG2 increases in response to low level of oxidative stress, whereas TG2 diminishes under high stress conditions. Monitoring TG2 expression, activity and calcium concentration in cells treated with A23187 revealed that the initial rise of calcium activates TG2 but subsequent calcium-overload induces the degradation of TG2 via calcium-mediated polyubiquitination. These results indicate that the role of TG2 in apoptosis depends on the level of calcium influx triggered by oxidative stress.

Structured summary

MINT-6824687: TG2 (uniprotkb:P21980) physically interacts (MI:0218) with Ubiquitin (uniprotkb:P62988) by anti bait coimmunoprecipitation (MI:0006)

Abbreviations: TG2, transglutaminase 2, UV, ultra violet, BP, biotinylated pentylamine, GAPDH, glyceraldehyde-3-phosphate dehydrogenase, HA, hemagglutinin, SA-HRP, horseradish peroxidase-conjugated streptavidin

Keywords: Transglutaminase 2, Oxidative stress, Ubiquitination, Proteasomal degradation, Calcium-overload

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PII: S0014-5793(09)00069-6

doi:10.1016/j.febslet.2009.01.032

FEBS Letters
Volume 583, Issue 4 , Pages 648-654, 18 February 2009