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Endogenous Cyclin D1 Promotes the Rate of Onset and Magnitude of Mitogenic Signaling via Akt1 Ser473 Phosphorylation
Journal article   Open access   Peer reviewed

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

Ke Chen, Xuanmao Jiao, Agnese Di Rocco, Duanwen Shen, Shaohua Xu, Adam Ertel, Zuoren Yu, Gabriele Di Sante, Min Wang, Zhiping Li, …
Cell reports (Cambridge), v 32(11), 108151
15 Sep 2020
DOI: https://doi.org/10.1016/j.celrep.2020.108151
PMID: 32937140
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/j.celrep.2020.108151View
Published, Version of Record (VoR)CC BY-NC-ND V4.0,  Open

Abstract

Akt1 breast cancer cyclin D1 phosphorylation
Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates RB and functions as a collaborative nuclear oncogene. The serine threonine kinase Akt plays a pivotal role in the control of cellular metabolism, survival, and mitogenic signaling. Herein, Akt1-mediated phosphorylation of downstream substrates in the mammary gland is reduced by cyclin D1 genetic deletion and is induced by mammary-gland-targeted cyclin D1 overexpression. Cyclin D1 is associated with Akt1 and augments the rate of onset and maximal cellular Akt1 activity induced by mitogens. Cyclin D1 is identified in a cytoplasmic-membrane-associated pool, and cytoplasmic-membrane-localized cyclin D1—but not nuclear-localized cyclin D1—recapitulates Akt1 transcriptional function. These studies identify a novel extranuclear function of cyclin D1 to enhance proliferative functions via augmenting Akt1 phosphorylation at Ser473. [Display omitted] •Cyclin D1 enhances Akt1 activities both in vitro and in vivo•Cyclin D1 bound to and phosphorylated Akt1 at Ser473•Cyclin D1 was required for growth factor induced Akt1 activity•Correlation of cyclin D1 and Akt1 gene signature with breast cancer patient outcomes Chen et al. show that the rate of onset and maximal cellular Akt1 activity induced by mitogens was augmented by cyclin D1. Cyclin D1 bound and phosphorylated Akt1 at Ser473. These studies identify a novel extranuclear function of cyclin D1 to enhance proliferative functions via augmenting Akt1 phosphorylation at Ser473.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Cell Biology
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