Ubiquitylation-dependent downregulation of Nck regulates its functional activity

FEBS Lett. 2014 Nov 3;588(21):3808-15. doi: 10.1016/j.febslet.2014.08.033. Epub 2014 Sep 16.

Abstract

The Nck adapter protein is involved in key cellular functions, such as actin polymerization and reorganization, serving as a molecular bridge between the surface complex essential for foreign antigen recognition, the T-cell antigen receptor (TCR), and the actin machinery. However, the mechanisms regulating Nck expression and functions are unknown. In this study, we revealed Nck negative regulation and demonstrated that Nck is ubiquitylated following cellular activation. We identified the molecular determinants and mediators involved in this process. Our data suggest that Nck ubiquitylation might serve as a mechanism controlling Nck-mediated effector functions during cellular activation.

Keywords: Actin machinery; Nck; T-cell signaling; Ubiquitylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Adhesion
  • Down-Regulation*
  • Gene Silencing
  • HEK293 Cells
  • Humans
  • Jurkat Cells
  • Mutation
  • Oncogene Proteins / chemistry
  • Oncogene Proteins / deficiency
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteolysis
  • Proto-Oncogene Proteins c-cbl / metabolism
  • RNA, Small Interfering / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Ubiquitination*
  • src Homology Domains

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • Nck protein
  • Oncogene Proteins
  • RNA, Small Interfering
  • Receptors, Antigen, T-Cell
  • Proto-Oncogene Proteins c-cbl
  • Proteasome Endopeptidase Complex