RINGO/Speedy proteins, a family of non-canonical activators of CDK1 and CDK2

Semin Cell Dev Biol. 2020 Nov:107:21-27. doi: 10.1016/j.semcdb.2020.03.010. Epub 2020 Apr 18.

Abstract

Cyclin-dependent kinases (CDKs) require the binding to a regulatory subunit to acquire enzymatic activity, and cyclins are the canonical CDK activators. However, there are specific situations in which CDKs can be activated by non-cyclin proteins that are less characterized. This review focuses on the family of RINGO/Speedy proteins, which have no sequence amino acid homology to cyclins but can bind to and activate CDK1 and CDK2. Interestingly, RINGO/Speedy proteins can activate CDKs under conditions in which CDK-cyclin complexes would not be active, and there is evidence that RINGO/Speedy-activated CDKs can phosphorylate different sites than the cyclin-activated CDKs. RINGO/Speedy proteins were originally described in Xenopus oocytes, but their roles in mammalian cells have also been addressed. We will summarize the properties of RINGO/Speedy proteins and how they trigger CDK activation, and discuss recent studies that characterized their physiological functions. In particular, studies using genetically modified mice have shown that RingoA, also known as Spy1, plays a key role in meiosis regulation. Emerging evidence also suggests a potential role for RingoA/Spy1 in cancer.

Keywords: CDK activator; Cancer; Meiosis; RINGO; Speedy; Telomere.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism*
  • Cyclin-Dependent Kinases / metabolism*
  • DNA Damage
  • Enzyme Activation
  • Humans
  • Meiosis
  • Neoplasms / metabolism
  • Neoplasms / pathology

Substances

  • Cell Cycle Proteins
  • Cyclin-Dependent Kinases