Related Experiment Video

Updated: Dec 8, 2025

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

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Endogenous Cyclin D1 Promotes the Rate of Onset and Magnitude of Mitogenic Signaling via Akt1 Ser473 Phosphorylation

Ke Chen1, Xuanmao Jiao2, Agnese Di Rocco2

  • 1Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Bluemle Life Sciences Building, 233 South 10(th) Street, Philadelphia, PA 19107, USA.

Cell Reports
|September 16, 2020
PubMed

Insights

Cyclin D1 enhances Akt1 activity and cellular proliferation by phosphorylating Akt1 at Ser473. This extranuclear function of cyclin D1 is crucial for mitogenic signaling and mammary gland growth.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Oncology

Background:

  • Cyclin D1 is a regulatory subunit of a holoenzyme that phosphorylates RB and acts as a nuclear oncogene.
  • The serine threonine kinase Akt is critical for cellular metabolism, survival, and mitogenic signaling.

Purpose of the Study:

  • To investigate the role of cyclin D1 in regulating Akt1 activity and function in the mammary gland.
  • To identify the subcellular localization and specific functions of cyclin D1 in relation to Akt1.

Main Methods:

  • Genetic manipulation of cyclin D1 in mammary glands (deletion and overexpression).
  • Assessing Akt1-mediated phosphorylation of downstream substrates.
  • Investigating the association between cyclin D1 and Akt1.
  • Analyzing the subcellular localization of cyclin D1 (cytoplasmic-membrane vs. nuclear).

Main Results:

  • Cyclin D1 genetic deletion reduced Akt1-mediated phosphorylation, while overexpression induced it in mammary glands.
  • Cyclin D1 associates with Akt1, augmenting mitogen-induced Akt1 activity.
  • Cytoplasmic-membrane-localized cyclin D1, but not nuclear-localized cyclin D1, recapitulates Akt1 transcriptional function.
  • Cyclin D1 enhances Akt1 phosphorylation at Ser473.

Conclusions:

  • Cyclin D1 possesses a novel extranuclear function that enhances proliferative functions.
  • This enhancement is mediated by augmenting Akt1 phosphorylation at Ser473, highlighting a new mechanism in mitogenic signaling.
Keywords:
Akt1breast cancercyclin D1phosphorylation

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