Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer

Nat Rev Cancer. 2008 Jun;8(6):438-49. doi: 10.1038/nrc2396.

Abstract

The maintenance and preservation of distinct phases during the cell cycle is a highly complex and coordinated process. It is regulated by phosphorylation--through the activity of cyclin-dependent kinases (CDKs)--and protein degradation, which occurs through ubiquitin ligases such as SCF (SKP1-CUL1-F-box protein) complexes and APC/C (anaphase-promoting complex/cyclosome). Here, we explore the functionality and biology of the F-box proteins, SKP2 (S-phase kinase-associated protein 2) and beta-TrCP (beta-transducin repeat-containing protein), which are emerging as important players in cancer biogenesis owing to the deregulated proteolysis of their substrates.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Cycle Proteins / physiology
  • Co-Repressor Proteins
  • Cullin Proteins / physiology
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Cyclin-Dependent Kinases / metabolism
  • DNA-Binding Proteins / metabolism
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / metabolism
  • Humans
  • NF-kappa B / metabolism
  • Neoplasm Proteins / metabolism*
  • Neoplasms / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Oncogenes
  • RNA-Binding Proteins / metabolism
  • Repressor Proteins / metabolism
  • S-Phase Kinase-Associated Proteins / physiology*
  • SKP Cullin F-Box Protein Ligases / physiology
  • beta-Transducin Repeat-Containing Proteins / physiology*
  • cdc25 Phosphatases / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • Co-Repressor Proteins
  • Cullin 1
  • Cullin Proteins
  • DNA-Binding Proteins
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • NF-kappa B
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • PDCD4 protein, human
  • RCOR1 protein, human
  • RNA-Binding Proteins
  • Repressor Proteins
  • S-Phase Kinase-Associated Proteins
  • beta-Transducin Repeat-Containing Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • SKP Cullin F-Box Protein Ligases
  • Cyclin-Dependent Kinases
  • CDC25A protein, human
  • cdc25 Phosphatases