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Updated: May 24, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Human cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) is dimeric in its disulfide-reduced state, with

Asli Ertekin1, James M Aramini, Paolo Rossi

  • 1Center for Advanced Biotechnology and Medicine and Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.

The Journal of Biological Chemistry
|March 20, 2012
PubMed

Insights

Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) functions as a tumor suppressor and cell cycle regulator. Its solution structure reveals an intrinsically disordered N-terminal region and a four-helix bundle, crucial for its function.

Area of Science:

  • Structural Biology
  • Molecular Biology
  • Cancer Research

Background:

  • CDK2AP1 (deleted in oral cancer 1) is a tumor suppressor protein involved in cell cycle regulation.
  • Its absence or downregulation is observed in various cancer types, highlighting its significance.
  • CDK2AP1 is the sole known specific inhibitor of CDK2, critical for the G1-to-S phase transition.

Purpose of the Study:

  • To determine the solution structure of CDK2AP1.
  • To elucidate the structural basis of CDK2AP1's function in cell cycle regulation and tumor suppression.

Main Methods:

  • Solution Nuclear Magnetic Resonance (NMR) spectroscopy.
  • Amide hydrogen/deuterium exchange measurements coupled with mass spectrometry.

Main Results:

  • The homodimeric structure of CDK2AP1 was elucidated.
  • It features an intrinsically disordered N-terminal region (60 residues) and a C-terminal four-helix bundle.
  • Cys-105 residues are positioned for potential disulfide bond formation, and Ser-46 is phosphorylated by IκB kinase ε.

Conclusions:

  • The determined structure provides insights into CDK2AP1's mechanism as a cell cycle regulator and tumor suppressor.
  • The intrinsically disordered region and specific phosphorylation site are key features for its biological activity.
  • Structural understanding may facilitate the development of targeted cancer therapies.

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