The E3 ubiquitin ligase CHIP binds the androgen receptor in a phosphorylation-dependent manner

Biochim Biophys Acta. 2006 Jun;1764(6):1073-9. doi: 10.1016/j.bbapap.2006.03.013. Epub 2006 Apr 4.

Abstract

In Eukarya, the 26S proteasome is primarily responsible for intracellular protein degradation. To be degraded, proteins must be ubiquitinated. The latter requires a multi-enzyme cascade consisting of an E1, an E2, and an E3 enzyme. While there is only a single E1 and a few E2s, there are many different E3s that target substrates by recognizing specific sequence motifs, known as degrons. Here, we have used the peptide array technology to identify binding motifs in the human androgen receptor (AR), which are recognized by the Carboxyl-terminus of Hsc70-Interacting Protein (CHIP), a U-box E3 and Hsp70/Hsp90 co-chaperone. We show that CHIP recognizes AR in a highly specific, phosphorylation- and sequence-dependent manner, and propose that this interaction could provide a mechanism that regulates the degradation of CHIP substrates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • HSP90 Heat-Shock Proteins / chemistry
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphorylation
  • Proteasome Endopeptidase Complex / chemistry
  • Receptors, Androgen / chemistry*
  • Ubiquitin-Protein Ligases / chemistry*

Substances

  • HSP90 Heat-Shock Proteins
  • Receptors, Androgen
  • STUB1 protein, human
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease