Ubiquitination-dependent degradation of p73 by the mitochondrial E3 ubiquitin ligase Hades

被引：11

作者：

Min, Bumki ^{[1
]}

Ryu, Jiwon ^{[1
]}

Chi, Seung-Wook ^{[2
]}

Yi, Gwan-Su ^{[1
]}

机构：

[1] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Taejon 305701, South Korea

[2] KRIBB, Struct Biol & Nanopore Res Lab, Taejon 305806, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 467卷 / 02期

基金：

新加坡国家研究基金会;

关键词：

p73; Hades; RING-finger domain; Ubiquitination; Mitochondria; P53; PROTEIN; TUMOR-SUPPRESSOR; APOPTOSIS; TRANSACTIVATION; STABILITY; DOMAIN; TAP73; DELTA-NP73; MECHANISM; PATHWAY;

D O I：

10.1016/j.bbrc.2015.09.163

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

p73 is a member of the p53 family of transcription factors which plays an essential role in tumor suppression. p73 is associated with the sensitivity of cancer cells to chemotherapy and the prognosis of many cancers. In this study, we showed the ubiquitination-dependent degradation of p73 by the mitochondrial E3 ubiquitin ligase Hades. First, the binding between p73 and Hades was identified by coimmunoprecipitation experiments, and it was found that the Hades RING-finger domain mediates the interaction with p73. Immunofluorescence analysis showed that p73 moves to the mitochondria and colocalizes with Hades during etoposide-induced apoptosis. By performing in vivo and in vitro ubiquitination assays, we observed that the Hades RING-finger domain promotes ubiquitination of p73. Finally, it was shown that SiRNA-mediated depletion of Hades stabilizes p73. Taken together, our results showed that Hades mediates the ubiquitination-dependent degradation of mitochondrial p73 under apoptotic conditions. These findings suggest that Hades-mediated p73 ubiquitination is a novel regulatory mechanism for the exonuclear function of p73. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：316 / 321

页数：6

共 42 条

[11] The antiapoptotic DeltaNp73 is degraded in a c-Jun-dependent manner upon genotoxic stress through the antizyme-mediated pathway [J].

Dulloo, Iqbal ;

Gopalan, Ganesan ;

Melino, Gerry ;

Sabapathy, Kanaga .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (11) :4902-4907

[12] Dual-site Interactions of p53 Protein Transactivation Domain with Anti-apoptotic Bcl-2 Family Proteins Reveal a Highly Convergent Mechanism of Divergent p53 Pathways [J].

Ha, Ji-Hyang ;

Shin, Jae-Sun ;

Yoon, Mi-Kyung ;

Lee, Min-Sung ;

He, Fahu ;

Bae, Kwang-Hee ;

Yoon, Ho Sup ;

Lee, Chong-Kil ;

Park, Sung Goo ;

Muto, Yutaka ;

Chi, Seung-Wook .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (10) :7387-7398

[13] p53 family genes: structural comparison, expression and mutation [J].

Ikawa, S ;

Nakagawara, A ;

Ikawa, Y .

CELL DEATH AND DIFFERENTIATION, 1999, 6 (12) :1154-1161

[14] TAp73 is required for spermatogenesis and the maintenance of male fertility [J].

Inoue, Satoshi ;

Tomasini, Richard ;

Rufini, Alessandro ;

Elia, Andrew J. ;

Agostini, Massimiliano ;

Amelio, Ivano ;

Cescon, Dave ;

Dinsdale, David ;

Zhou, Lily ;

Harris, Isaac S. ;

Lac, Sophie ;

Silvester, Jennifer ;

Li, Wanda Y. ;

Sasaki, Masato ;

Haight, Jillian ;

Bruestle, Anne ;

Wakeham, Andrew ;

Mckerlie, Colin ;

Jurisicova, Andrea ;

Melino, Gerry ;

Mak, Tak W. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (05) :1843-1848

[15] Mitochondrially localised MUL1 is a novel modulator of antiviral signaling [J].

Jenkins, Kristie ;

Khoo, Jing Jing ;

Sadler, Anthony ;

Piganis, Rebecca ;

Wang, Die ;

Borg, Natalie A. ;

Hjerrild, Kathryn ;

Gould, Jodee ;

Thomas, Belinda J. ;

Nagley, Phillip ;

Hertzog, Paul J. ;

Mansell, Ashley .

IMMUNOLOGY AND CELL BIOLOGY, 2013, 91 (04) :321-330

[16] E3 ubiquitin ligase Hades negatively regulates the exonuclear function of p53 [J].

Jung, J. H. ;

Bae, S. ;

Lee, J. Y. ;

Woo, S. R. ;

Cha, H. J. ;

Yoon, Y. ;

Suh, K-S ;

Lee, S-J ;

Park, I-C ;

Jin, Y-W ;

Lee, K-H ;

An, S. ;

Lee, J. H. .

CELL DEATH AND DIFFERENTIATION, 2011, 18 (12) :1865-1875

[17] The p73 Tumor Suppressor Is Targeted by Pirh2 RING Finger E3 Ubiquitin Ligase for the Proteasome-dependent Degradation [J].

Jung, Yong-Sam ;

Qian, Yingjuan ;

Chen, Xinbin .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (41) :35388-35395

[18] Genome-Wide and Functional Annotation of Human E3 Ubiquitin Ligases Identifies MULAN, a Mitochondrial E3 that Regulates the Organelle's Dynamics and Signaling [J].

Li, Wei ;

Bengtson, Mario H. ;

Ulbrich, Axel ;

Matsuda, Akio ;

Reddy, Venkateshwar A. ;

Orth, Anthony ;

Chanda, Sumit K. ;

Batalov, Serge ;

Joazeiro, Claudio A. P. .

PLOS ONE, 2008, 3 (01)

[19] Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans [J].

Linke, K. ;

Mace, P. D. ;

Smith, C. A. ;

Vaux, D. L. ;

Silke, J. ;

Day, C. L. .

CELL DEATH AND DIFFERENTIATION, 2008, 15 (05) :841-848

[20] Cooperative role of RanBP9 and P73 in mitochondria-mediated apoptosis [J].

Liu, T. ;

Roh, S. E. ;

Woo, J. A. ;

Ryu, H. ;

Kang, D. E. .

CELL DEATH & DISEASE, 2013, 4 :e476-e476

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