The testis-specific USP26 is a deubiquitinating enzyme of the ubiquitin ligase Mdm2

Shirly Lahav-Baratz, Yelena Kravtsova-Ivantsiv, Shay Golan, Aaron Ciechanover

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

Murine double minute-2 (Mdm2) is one of the E3-ligases of the androgen receptor besides being the major regulator of the p53 tumor suppressor. The testis-specific USP26 was demonstrated to regulate the androgen receptor. In the present study we examined possible association between the deubiquitinating enzyme - ubiquitin specific protease 26 (USP26), and the oncoprotein E3 ligase - (Mdm-2). We analyzed the half-life time of USP26 in HEK293 cells. In a cell-free system we asked whether USP26 can be ubiquitinated by HeLa extract. In co-transfection experiments we expressed Mdm2 along with different constructs of USP26 in order to examine possible regulation of Mdm2 by USP26. We found that USP26 binds to Mdm2 through its coiled-coiled C-terminal domain. USP26 deubiquitinates Mdm2 and stabilizes it. The physiological significance of the findings is still not fully understood. The interaction between USP26 and Mdm2, and the subsequent deubiquitination of Mdm2, serves, most probably to regulate Mdm2. Future therapeutic modalities that interfere with the association between USP26 and Mdm2 will be used to destabilize the ligase in malignancies where it is upregulated.

Original languageEnglish
Pages (from-to)106-111
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume482
Issue number1
DOIs
StatePublished - 1 Jan 2017

Fingerprint

Ubiquitin-Specific Proteases
Ligases
Ubiquitin
Testis
Enzymes
Ubiquitin-Protein Ligases
Androgen Receptors
Deubiquitinating Enzymes
Cell-Free System
Oncogene Proteins
Transfection
Half-Life
Tumors
Neoplasms

Keywords

  • DUB
  • Male infertility
  • Mdm2
  • Spermatozoa
  • USP26

Cite this

Lahav-Baratz, Shirly ; Kravtsova-Ivantsiv, Yelena ; Golan, Shay ; Ciechanover, Aaron. / The testis-specific USP26 is a deubiquitinating enzyme of the ubiquitin ligase Mdm2. In: Biochemical and Biophysical Research Communications. 2017 ; Vol. 482, No. 1. pp. 106-111.
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The testis-specific USP26 is a deubiquitinating enzyme of the ubiquitin ligase Mdm2. / Lahav-Baratz, Shirly; Kravtsova-Ivantsiv, Yelena; Golan, Shay; Ciechanover, Aaron.

In: Biochemical and Biophysical Research Communications, Vol. 482, No. 1, 01.01.2017, p. 106-111.

Research output: Contribution to journalArticleResearchpeer-review

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