CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling.

The EMBO Journal
Si-Han ChenNevan J Krogan

Abstract

Multi-subunit cullin-RING ligases (CRLs) are the largest family of ubiquitin E3 ligases in humans. CRL activity is tightly regulated to prevent unintended substrate degradation or autocatalytic degradation of CRL subunits. Using a proteomics strategy, we discovered that CRL4AMBRA1 (CRL substrate receptor denoted in superscript) targets Elongin C (ELOC), the essential adapter protein of CRL5 complexes, for polyubiquitination and degradation. We showed that the ubiquitin ligase function of CRL4AMBRA1 is required to disrupt the assembly and attenuate the ligase activity of human CRL5SOCS3 and HIV-1 CRL5VIF complexes as AMBRA1 depletion leads to hyperactivation of both CRL5 complexes. Moreover, CRL4AMBRA1 modulates interleukin-6/STAT3 signaling and HIV-1 infectivity that are regulated by CRL5SOCS3 and CRL5VIF, respectively. Thus, by discovering a substrate of CRL4AMBRA1, ELOC, the shared adapter of CRL5 ubiquitin ligases, we uncovered a novel CRL cross-regulation pathway.

References

Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·J M Galan, M Peter
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·J G ZhangN A Nicola
May 17, 2003·Science·Denise LecossierAllan J Hance
May 20, 2003·Nature Immunology·Ben A CrokerWarren S Alexander
May 20, 2003·Nature Immunology·Roland LangPeter J Murray
Oct 23, 2003·Annual Review of Cell and Developmental Biology·Linda Hicke, Rebecca Dunn
Feb 3, 2005·Nature Reviews. Molecular Cell Biology·Matthew D Petroski, Raymond J Deshaies
May 26, 2007·Nature Reviews. Immunology·Akihiko YoshimuraMasato Kubo
Jun 26, 2007·Nature·Gian Maria FimiaFrancesco Cecconi
May 27, 2008·Nature Reviews. Cancer·David Frescas, Michele Pagano
Sep 23, 2008·Nature Biotechnology·Robin NathansTariq M Rana
Jul 21, 2009·Cell·Mathew E SowaJ Wade Harper
Sep 15, 2009·Molecular Cell·Michael W SchmidtDieter A Wolf
Oct 24, 2009·Nature Reviews. Cancer·Hua YuRichard Jove
Aug 17, 2010·Methods : a Companion to Methods in Enzymology·Stefanie JägerNevan J Krogan
Aug 24, 2011·Nature Reviews. Molecular Cell Biology·Allan M WeissmanAaron Ciechanover
Sep 13, 2011·Molecular Cell·Woong KimSteven P Gygi
Nov 15, 2011·Current Biology : CB·Ian T FoeDavid P Toczyski
Dec 23, 2011·Nature·Stefanie JägerNevan J Krogan
Dec 23, 2011·Nature·Stefanie JägerNevan J Krogan
Sep 11, 2012·Cell Reports·Radoslav I EnchevEdward P Morris
Jan 5, 2013·Science·Le CongFeng Zhang
Aug 27, 2013·The EMBO Journal·Pengyan XiaZusen Fan

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Citations

May 28, 2019·Cells·Monica Vara-PerezPatrizia Agostinis
Sep 9, 2021·DNA and Cell Biology·Andrea C ChaikovskyDaniele Simoneschi

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