MEX is a testis-specific E3 ubiquitin ligase that promotes death receptor-induced apoptosis

The Biochemical Journal
Yasumasa NishitoGabriel Núñez

Abstract

In the present study, we report the identification and characterization of MEX (MEKK1-related protein X), a protein with homology to MEKK1 that is expressed uniquely in the testis. MEX is comprises four putative zinc-binding domains including an N-terminal SWIM (SWI2/SNF2 and MuDR) domain of unknown function and two RING (really interesting new gene) fingers separated by a ZZ zinc finger domain. Biochemical analyses revealed that MEX is self-ubiquitinated and targeted for degradation through the proteasome pathway. MEX can act as an E3, Ub (ubiquitin) ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c or UbcH6. A region of MEX that contains the RING fingers and the ZZ zinc finger was required for interaction with UbcH5a and MEX self-association, whereas the SWIM domain was critical for MEX ubiquitination. The expression of MEX promoted apoptosis that was induced through Fas, DR (death receptor) 3 and DR4 signalling, but not that mediated by the BH3 (Bcl-2 homology 3)-only protein BimEL or the chemotherapeutic drug adriamycin. The enhancement of apoptosis by MEX required a functional SWIM domain, suggesting that MEX ubiquitination is critical for the enhancement of apoptosis. These results indicate that MEX acts as an...Continue Reading

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Citations

Aug 30, 2011·Molecular Biology and Evolution·Astrid BöhneJean-Nicolas Volff
Jul 27, 2010·Asian Journal of Andrology·Yun-Qiang LiuSi-Zhong Zhang
Jun 20, 2007·Archives of Biochemistry and Biophysics·Hong NianChunsheng Han
Dec 11, 2007·Biochimica Et Biophysica Acta·Elissa W P WongC Yan Cheng
May 16, 2012·The Biochemical Journal·Michael A RiegerBruce D Cuevas
Mar 19, 2014·Seminars in Cell & Developmental Biology·John H RichburgShawn B Bratton
Dec 2, 2017·Environmental Microbiology·Lana J McMillanJulie A Maupin-Furlow
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Dec 12, 2012·Molecular Biology Reports·Han LuBuwei Yu
May 23, 2014·Journal of Biosciences·Chiu-Jung HuangKong Bung Choo
Dec 27, 2012·Molecular Biology Reports·Cong-Cong Hou, Wan-Xi Yang
Sep 30, 2020·Disease Models & Mechanisms·Zakia AbdelhamedRolf W Stottmann

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