Emerging role of DYRK family protein kinases as regulators of protein stability in cell cycle control

Cell Cycle. 2012 Sep 15;11(18):3389-94. doi: 10.4161/cc.21404. Epub 2012 Aug 23.

Abstract

Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) constitute an evolutionarily conserved family of protein kinases with key roles in the control of cell proliferation and differentiation. Members of the DYRK family phosphorylate many substrates, including critical regulators of the cell cycle. A recent report revealed that human DYRK2 acts as a negative regulator of G1/S transition by phosphorylating c-Jun and c-Myc, thereby inducing ubiquitination-mediated degradation. Other DYRKs also function as cell cycle regulators by modulating the turnover of their target proteins. DYRK1B can induce reversible cell arrest in a quiescent G0 state by targeting cyclin D1 for proteasomal degradation and stabilizing p27 (Kip1). The DYRK2 ortholog of C. elegans, MBK-2, triggers the proteasomal destruction of oocyte proteins after meiosis to allow the mitotic divisions in embryo development. This review summarizes the accumulating results that provide evidence for a general role of DYRKs in the regulation of protein stability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle Checkpoints*
  • Humans
  • Models, Biological
  • Protein Stability*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*
  • Proteolysis
  • Ubiquitination

Substances

  • Dyrk kinase
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases