The ubiquitin ligase HERC4 mediates c-Maf ubiquitination and delays the growth of multiple myeloma xenografts in nude mice.

Blood
Zubin ZhangXinliang Mao

Abstract

The transcription factor c-Maf is extensively involved in the pathophysiology of multiple myeloma (MM), a fatal malignancy of plasma cells. In the present study, affinity chromatography and mass spectrometry were used to identify c-Maf ubiquitination-associated proteins, from which the E3 ligase HERC4 was found to interact with c-Maf and catalyzed its polyubiquitination and subsequent proteasome-mediated degradation. HERC4 mediated polyubiquitination at K85 and K297 in c-Maf, and this polyubiquitination could be prevented by the isopeptidase USP5. Further analysis on the NCI-60 cell line collection revealed that RPMI 8226, a MM-derived cell line, expressed the lowest level of HERC4. Primary bone marrow analysis revealed HERC4 expression was high in normal bone marrow, but was steadily decreased during myelomagenesis. These findings suggested HERC4 played an important role in MM progression. Moreover, ectopic HERC4 expression decreased MM proliferation in vitro, and delayed xenograft tumor growth in vivo. Therefore, modulation of c-Maf ubiquitination by targeting HERC4 may represent a new therapeutic modality for MM.

References

Oct 9, 2002·The Journal of Biological Chemistry·Kohsuke KataokaHiroshi Handa
Apr 20, 2004·Blood·Teru HideshimaKenneth C Anderson
Jan 21, 2006·Cancer Research·Naoki MoritoSatoru Takahashi
Oct 31, 2007·Developmental Biology·Clara I Rodriguez, Colin L Stewart
Jan 15, 2009·Nature Reviews. Cancer·Alain EychèneCelio Pouponnot
Jun 26, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jianmei W LeavenworthMary E Pauza
Feb 4, 2010·European Journal of Immunology·Bo-Shiou LinShi-Chuen Miaw
Mar 16, 2011·The Journal of Biological Chemistry·Kojiro SatoToshihide Mimura
Jul 17, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chen-Yen LaiShi-Chuen Miaw
Jul 5, 2013·PloS One·Jiefei TongMichael F Moran
Nov 15, 2013·Cancer Cell International·Hui ZhouWen-Li Ma
Dec 3, 2014·The International Journal of Biochemistry & Cell Biology·Guodong ChenXinliang Mao
Feb 17, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Wen-Li ZengRong Shi

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Citations

Mar 17, 2017·Anti-cancer Drugs·Hongwu MaoXinliang Mao
Dec 12, 2019·The Journal of Biological Chemistry·Yuanming HeXinliang Mao
Jul 5, 2017·Journal of Hematology & Oncology·Yujia XuXinliang Mao
Jun 15, 2019·Acta Pharmacologica Sinica·Xue-Han ChenTie Zhang
Jul 31, 2018·The Journal of Clinical Investigation·Chao-Yuan HsuHuey-Kang Sytwu
May 7, 2020·International Journal of Molecular Sciences·Chao-Yuan HsuHuey-Kang Sytwu
Jun 26, 2020·Cancers·Joan Sala-GastonJose Luis Rosa
Dec 31, 2020·Clinical and Translational Medicine·Mengqing XiaoKe Cao
Feb 26, 2021·Cell Communication and Signaling : CCS·Tong SunXinliang Mao
Sep 19, 2020·European Journal of Pharmacology·Yaqiong ZhuMeiqun Wang
Aug 21, 2021·The Journal of Biological Chemistry·Yuanming HeXinliang Mao
Aug 30, 2021·Biomarker Research·Hu LeiYingli Wu

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