Document Type
Article
Publication Date
9-15-2020
Abstract
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.
Recommended Citation
Chen, Ke; Jiao, Xuanmao; Di Rocco, Agnese; Shen, Duanwen; Xu, Shaohua; Ertel, Adam; Yu, Zuoren; Di Sante, Gabriele; Wang, Min; Li, Zhiping; Pestell, Timothy G; Casimiro, Mathew C; Skordalakes, Emmanuel; Achilefu, Samuel; and Pestell, Richard G, "Endogenous Cyclin D1 Promotes the Rate of Onset and Magnitude of Mitogenic Signaling via Akt1 Ser473 Phosphorylation." (2020). Department of Cancer Biology Faculty Papers. Paper 170.
https://jdc.jefferson.edu/cbfp/170
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
PubMed ID
32937140
Language
English
Comments
This article is the author’s final published version in Cell Reports, Volume 32, Issue 11, September 2020, Article number 108151.
The published version is available at https://doi.org/10.1016/j.celrep.2020.108151. Copyright © Chen