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Journal article
Endogenous Cyclin D1 Promotes the Rate of Onset and Magnitude of Mitogenic Signaling via Akt1 Ser473 Phosphorylation
Cell reports (Cambridge), v 32(11), 108151
15 Sep 2020
PMID: 32937140
Featured in Collection : UN Sustainable Development Goals @ Drexel
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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•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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- Title
- Endogenous Cyclin D1 Promotes the Rate of Onset and Magnitude of Mitogenic Signaling via Akt1 Ser473 Phosphorylation
- Creators
- Ke Chen - Kimmel Cancer CenterXuanmao Jiao - Baruch S. Blumberg InstituteAgnese Di Rocco - Baruch S. Blumberg InstituteDuanwen Shen - Washington University in St. LouisShaohua Xu - Kimmel Cancer CenterAdam Ertel - Sidney Kimmel Cancer CenterZuoren Yu - Tongji UniversityGabriele Di Sante - Baruch S. Blumberg InstituteMin Wang - Baruch S. Blumberg InstituteZhiping Li - Baruch S. Blumberg InstituteTimothy G. Pestell - Kimmel Cancer CenterMathew C. Casimiro - Abraham Baldwin Agricultural CollegeEmmanuel Skordalakes - The Wistar InstituteSamuel Achilefu - Washington University in St. LouisRichard G. Pestell - The Wistar Institute
- Publication Details
- Cell reports (Cambridge), v 32(11), 108151
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000570646200021
- Scopus ID
- 2-s2.0-85090729403
- Other Identifier
- 991019176797004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology