CSNAP Is a Stoichiometric Subunit of the COP9 Signalosome

Cell Rep. 2015 Oct 20;13(3):585-598. doi: 10.1016/j.celrep.2015.09.021. Epub 2015 Oct 8.

Abstract

The highly conserved COP9 signalosome (CSN) complex is a key regulator of all cullin-RING-ubiquitin ligases (CRLs), the largest family of E3 ubiquitin ligases. Until now, it was accepted that the CSN is composed of eight canonical components. Here, we report the discovery of an additional integral and stoichiometric subunit that had thus far evaded detection, and we named it CSNAP (CSN acidic protein). We show that CSNAP binds CSN3, CSN5, and CSN6, and its incorporation into the CSN complex is mediated through the C-terminal region involving conserved aromatic residues. Moreover, depletion of this small protein leads to reduced proliferation and a flattened and enlarged morphology. Finally, on the basis of sequence and structural properties shared by both CSNAP and DSS1, a component of the related 19S lid proteasome complex, we propose that CSNAP, the ninth CSN subunit, is the missing paralogous subunit of DSS1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism
  • Amino Acid Sequence
  • COP9 Signalosome Complex
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Molecular Sequence Data
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Peptide Hydrolases / chemistry
  • Peptide Hydrolases / metabolism*
  • Protein Binding
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism
  • Protein Multimerization

Substances

  • Adaptor Proteins, Signal Transducing
  • COPS6 protein, human
  • COPS9 protein, human
  • Carrier Proteins
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • Protein Kinases
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex