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.
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.
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