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

  • Author(s): Chen, Si-Han
  • Jang, Gwendolyn M
  • Hüttenhain, Ruth
  • Gordon, David E
  • Du, Dan
  • Newton, Billy W
  • Johnson, Jeffrey R
  • Hiatt, Joseph
  • Hultquist, Judd F
  • Johnson, Tasha L
  • Liu, Yi-Liang
  • Burton, Lily A
  • Ye, Jordan
  • Reichermeier, Kurt M
  • Stroud, Robert M
  • Marson, Alexander
  • Debnath, Jayanta
  • Gross, John D
  • Krogan, Nevan J
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pubmed/?term=30166453%5Buid%5D
No data is associated with this publication.
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 CRL4AMBRA 1 (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 CRL4AMBRA 1 is required to disrupt the assembly and attenuate the ligase activity of human CRL5SOCS 3 and HIV-1 CRL5VIF complexes as AMBRA1 depletion leads to hyperactivation of both CRL5 complexes. Moreover, CRL4AMBRA 1 modulates interleukin-6/STAT3 signaling and HIV-1 infectivity that are regulated by CRL5SOCS 3 and CRL5VIF, respectively. Thus, by discovering a substrate of CRL4AMBRA 1, ELOC, the shared adapter of CRL5 ubiquitin ligases, we uncovered a novel CRL cross-regulation pathway.

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