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D-type cyclins

C J Sherr1

  • 1Howard Hughes Medical Institute, Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Trends in Biochemical Sciences
|May 1, 1995
PubMed
Summary

D-type cyclins, essential for cell cycle progression, link growth signals to DNA replication readiness. They activate cyclin-dependent kinases (CDKs) to drive cells through the G1 phase, ensuring commitment to cell division.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • D-type cyclins integrate extracellular growth factor signals with intracellular cell cycle machinery.
  • They are crucial for regulating the G1 phase of the mammalian cell division cycle.

Purpose of the Study:

  • To elucidate the role of D-type cyclins in coupling extracellular signals to cell cycle progression.
  • To understand how D-type cyclins facilitate the transition from G1 to S phase.

Main Methods:

  • The study focuses on the assembly of D-type cyclins with cyclin-dependent kinases (CDKs) 4 and 6.
  • It examines the phosphorylation of key substrates like the retinoblastoma protein.
  • Inhibitor roles and cell cycle progression past the G1 restriction point are considered.

Main Results:

  • D-type cyclins form active holoenzymes with CDK4/CDK6 upon growth factor stimulation.
  • These holoenzymes phosphorylate substrates, promoting G1 exit.
  • Antiproliferative signals induce inhibitors that counteract CDK activity.

Conclusions:

  • D-type cyclins are critical for sensing cell readiness for DNA replication.
  • They enforce commitment to enter S phase by facilitating G1 to S phase transition.
  • Their role is primarily to ensure proper entry into the DNA synthesis phase.

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