@article{aae27fecd71b43bcbe5908ae6d583e37,
title = "Endogenous Cyclin D1 Promotes the Rate of Onset and Magnitude of Mitogenic Signaling via Akt1 Ser473 Phosphorylation",
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.",
keywords = "Akt1, breast cancer, cyclin D1, phosphorylation",
author = "Ke Chen and Xuanmao Jiao and {Di Rocco}, Agnese and Duanwen Shen and Shaohua Xu and Adam Ertel and Zuoren Yu and {Di Sante}, Gabriele and Min Wang and Zhiping Li and Pestell, {Timothy G.} and Casimiro, {Mathew C.} and Emmanuel Skordalakes and Samuel Achilefu and Pestell, {Richard G.}",
note = "Funding Information: This work was supported in part by NIH R01CA132115 and the Breast Cancer Research Program (Breakthrough Award W81XWH1810605 ) (to R.G.P.), NIH R01CA201312-01 (to E.S.), and a Wistar Cancer Center support grant ( P30CA10815 , NIH) (to E.S. and R.G.P.). This work was partially funded by an American-Italian Cancer Foundation Post-Doctoral Research Fellowship (to G.D.S.). Funding Information: This work was supported in part by NIH R01CA132115 and the Breast Cancer Research Program (Breakthrough Award W81XWH1810605) (to R.G.P.), NIH R01CA201312-01 (to E.S.), and a Wistar Cancer Center support grant (P30CA10815, NIH) (to E.S. and R.G.P.). This work was partially funded by an American-Italian Cancer Foundation Post-Doctoral Research Fellowship (to G.D.S.). R.G.P. conceived, designed, and initiated the study and wrote the paper with X.J. and K.C.; K.C. and X.J. performed most of the experiments and, in concert with A.D.R. had primary responsibility for all experiments, analyzing all data, and writing the paper. S.X. and A.E. performed gene expression and statistical analysis of patient data. G.D.S. M.W. Z.L. and T.G.P. performed and analyzed tissue culture and transgenic experiments. M.C.C. and X.J. analyzed gene expression of RICTOR components in transgenic animals. E.S. conducted in silico analysis of cyclin D1/Akt1 interaction. M.W. provided extensive technical support for transgenics. D.S. and S.A. conducted the live cell Akt monitoring and contributed to the design of experiments involving those cells. All authors read, edited, and approved submission of the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = sep,
day = "15",
doi = "10.1016/j.celrep.2020.108151",
language = "English",
volume = "32",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",
}
