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; Timothy G. Pestell; Mathew C. Casimiro; Emmanuel Skordalakes; Samuel Achilefu; Richard G. Pestell

doi:10.1016/j.celrep.2020.108151

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, Timothy G. Pestell, Mathew C. Casimiro, Emmanuel Skordalakes, Samuel Achilefu, Richard G. Pestell

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Article number	108151
Journal	Cell Reports
Volume	32
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2020.108151
State	Published - Sep 15 2020
Externally published	Yes

Keywords

Akt1
breast cancer
cyclin D1
phosphorylation

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2020.108151

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Chen, K., Jiao, X., Di Rocco, A., Shen, D., Xu, S., Ertel, A., Yu, Z., Di Sante, G., Wang, M., Li, Z., Pestell, T. G., Casimiro, M. C., Skordalakes, E., Achilefu, S., & Pestell, R. G. (2020). Endogenous Cyclin D1 Promotes the Rate of Onset and Magnitude of Mitogenic Signaling via Akt1 Ser473 Phosphorylation. Cell Reports, 32(11), Article 108151. https://doi.org/10.1016/j.celrep.2020.108151

Chen, K, Jiao, X, Di Rocco, A, Shen, D, Xu, S, Ertel, A, Yu, Z, Di Sante, G, Wang, M, Li, Z, Pestell, TG, Casimiro, MC, Skordalakes, E, Achilefu, S & Pestell, RG 2020, 'Endogenous Cyclin D1 Promotes the Rate of Onset and Magnitude of Mitogenic Signaling via Akt1 Ser473 Phosphorylation', Cell Reports, vol. 32, no. 11, 108151. https://doi.org/10.1016/j.celrep.2020.108151

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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.",

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AU - Ertel, Adam

AU - Yu, Zuoren

AU - Di Sante, Gabriele

AU - Wang, Min

AU - Li, Zhiping

AU - Pestell, Timothy G.

AU - Casimiro, Mathew C.

AU - Skordalakes, Emmanuel

AU - Achilefu, Samuel

AU - Pestell, Richard G.

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

Abstract

Keywords

ASJC Scopus subject areas

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