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Mebendazole elicits potent antimyeloma activity by inhibiting the USP5/c-Maf axis.

Chen XH, Xu YJ, Wang XG, Lin P, Cao BY, Zeng YY, Wang Q, Zhang ZB, Mao XL, Zhang T.

Acta Pharmacol Sin. 2019 Jun 13. doi: 10.1038/s41401-019-0249-1. [Epub ahead of print]


Inhibition of the deubiquitinase USP5 leads to c-Maf protein degradation and myeloma cell apoptosis.

Wang S, Juan J, Zhang Z, Du Y, Xu Y, Tong J, Cao B, Moran MF, Zeng Y, Mao X.

Cell Death Dis. 2017 Sep 21;8(9):e3058. doi: 10.1038/cddis.2017.450.


The ubiquitin-conjugating enzyme UBE2O modulates c-Maf stability and induces myeloma cell apoptosis.

Xu Y, Zhang Z, Li J, Tong J, Cao B, Taylor P, Tang X, Wu D, Moran MF, Zeng Y, Mao X.

J Hematol Oncol. 2017 Jul 3;10(1):132. doi: 10.1186/s13045-017-0499-7.


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

Zhang Z, Tong J, Tang X, Juan J, Cao B, Hurren R, Chen G, Taylor P, Xu X, Shi CX, Du J, Hou J, Wang G, Wu D, Stewart AK, Schimmer AD, Moran MF, Mao X.

Blood. 2016 Mar 31;127(13):1676-86. doi: 10.1182/blood-2015-07-658203. Epub 2016 Jan 29.


The transmembrane protein TMEPAI induces myeloma cell apoptosis by promoting degradation of the c-Maf transcription factor.

Du Y, Liu Y, Xu Y, Juan J, Zhang Z, Xu Z, Cao B, Wang Q, Zeng Y, Mao X.

J Biol Chem. 2018 Apr 20;293(16):5847-5859. doi: 10.1074/jbc.RA117.000972. Epub 2018 Feb 21.


Ubiquitin specific peptidase 5 regulates colorectal cancer cell growth by stabilizing Tu translation elongation factor.

Xu X, Huang A, Cui X, Han K, Hou X, Wang Q, Cui L, Yang Y.

Theranostics. 2019 May 31;9(14):4208-4220. doi: 10.7150/thno.33803. eCollection 2019.


A chemical biology screen identifies glucocorticoids that regulate c-maf expression by increasing its proteasomal degradation through up-regulation of ubiquitin.

Mao X, Stewart AK, Hurren R, Datti A, Zhu X, Zhu Y, Shi C, Lee K, Tiedemann R, Eberhard Y, Trudel S, Liang S, Corey SJ, Gillis LC, Barber DL, Wrana JL, Ezzat S, Schimmer AD.

Blood. 2007 Dec 1;110(12):4047-54. Epub 2007 Sep 17.


Ubiquitination of the transcription factor c-MAF is mediated by multiple lysine residues.

Chen G, Xu X, Tong J, Han K, Zhang Z, Tang J, Li S, Yang C, Li J, Cao B, Zhou H, Wu D, Moran MF, Mao X.

Int J Biochem Cell Biol. 2014 Dec;57:157-66. doi: 10.1016/j.biocel.2014.10.024. Epub 2014 Oct 30.


Overexpression of USP5 contributes to tumorigenesis in non-small cell lung cancer via the stabilization of β-catenin protein.

Ma X, Qi W, Pan H, Yang F, Deng J.

Am J Cancer Res. 2018 Nov 1;8(11):2284-2295. eCollection 2018.


A mechanistic rationale for MEK inhibitor therapy in myeloma based on blockade of MAF oncogene expression.

Annunziata CM, Hernandez L, Davis RE, Zingone A, Lamy L, Lam LT, Hurt EM, Shaffer AL, Kuehl WM, Staudt LM.

Blood. 2011 Feb 24;117(8):2396-404. doi: 10.1182/blood-2010-04-278788. Epub 2010 Dec 16.


The deubiquitinating enzyme USP5 promotes pancreatic cancer via modulating cell cycle regulators.

Kaistha BP, Krattenmacher A, Fredebohm J, Schmidt H, Behrens D, Widder M, Hackert T, Strobel O, Hoheisel JD, Gress TM, Buchholz M.

Oncotarget. 2017 Aug 3;8(39):66215-66225. doi: 10.18632/oncotarget.19882. eCollection 2017 Sep 12.


ARK5 is transcriptionally regulated by the Large-MAF family and mediates IGF-1-induced cell invasion in multiple myeloma: ARK5 as a new molecular determinant of malignant multiple myeloma.

Suzuki A, Iida S, Kato-Uranishi M, Tajima E, Zhan F, Hanamura I, Huang Y, Ogura T, Takahashi S, Ueda R, Barlogie B, Shaughnessy J Jr, Esumi H.

Oncogene. 2005 Oct 20;24(46):6936-44.


Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma.

Hurt EM, Wiestner A, Rosenwald A, Shaffer AL, Campo E, Grogan T, Bergsagel PL, Kuehl WM, Staudt LM.

Cancer Cell. 2004 Feb;5(2):191-9.


Suppression of the deubiquitinating enzyme USP5 causes the accumulation of unanchored polyubiquitin and the activation of p53.

Dayal S, Sparks A, Jacob J, Allende-Vega N, Lane DP, Saville MK.

J Biol Chem. 2009 Feb 20;284(8):5030-41. doi: 10.1074/jbc.M805871200. Epub 2008 Dec 19.


USP5 promotes tumorigenesis and progression of pancreatic cancer by stabilizing FoxM1 protein.

Li XY, Wu HY, Mao XF, Jiang LX, Wang YX.

Biochem Biophys Res Commun. 2017 Oct 7;492(1):48-54. doi: 10.1016/j.bbrc.2017.08.040. Epub 2017 Aug 12.


A cell-permeant peptide corresponding to the cUBP domain of USP5 reverses inflammatory and neuropathic pain.

Garcia-Caballero A, Gadotti VM, Chen L, Zamponi GW.

Mol Pain. 2016 Apr 29;12. pii: 1744806916642444. doi: 10.1177/1744806916642444. Print 2016.


Smurf1 represses TNF-α production through ubiquitination and destabilization of USP5.

Qian G, Ren Y, Zuo Y, Yuan Y, Zhao P, Wang X, Cheng Q, Liu J, Zhang L, Guo T, Liu C, Zheng H.

Biochem Biophys Res Commun. 2016 Jun 3;474(3):491-496. doi: 10.1016/j.bbrc.2016.04.135. Epub 2016 Apr 29.


Usp5 links suppression of p53 and FAS levels in melanoma to the BRAF pathway.

Potu H, Peterson LF, Pal A, Verhaegen M, Cao J, Talpaz M, Donato NJ.

Oncotarget. 2014 Jul 30;5(14):5559-69.


Anthelmintic mebendazole enhances cisplatin's effect on suppressing cell proliferation and promotes differentiation of head and neck squamous cell carcinoma (HNSCC).

Zhang F, Li Y, Zhang H, Huang E, Gao L, Luo W, Wei Q, Fan J, Song D, Liao J, Zou Y, Liu F, Liu J, Huang J, Guo D, Ma C, Hu X, Li L, Qu X, Chen L, Yu X, Zhang Z, Wu T, Luu HH, Haydon RC, Song J, He TC, Ji P.

Oncotarget. 2017 Feb 21;8(8):12968-12982. doi: 10.18632/oncotarget.14673.


Mebendazole exhibits potent anti-leukemia activity on acute myeloid leukemia.

He L, Shi L, Du Z, Huang H, Gong R, Ma L, Chen L, Gao S, Lyu J, Gu H.

Exp Cell Res. 2018 Aug 1;369(1):61-68. doi: 10.1016/j.yexcr.2018.05.006. Epub 2018 May 8.


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