The membrane-associated form of cyclin D1 enhances cellular invasion
Abstract
The essential G1-cyclin, CCND1, is a collaborative nuclear oncogene that is frequently overexpressed in cancer. D-type cyclins bind and activate CDK4 and CDK6 thereby contributing to G1–S cell-cycle progression. In addition to the nucleus, herein cyclin D1 was also located in the cytoplasmic membrane. In contrast with the nuclear-localized form of cyclin D1 (cyclin D1NL), the cytoplasmic membrane-localized form of cyclin D1 (cyclin D1MEM) induced transwell migration and the velocity of cellular migration. The cyclin D1MEM was sufficient to induce G1–S cell-cycle progression, cellular proliferation, and colony formation. The cyclin D1MEM was sufficient to induce phosphorylation of the serine threonine kinase Akt (Ser473) and augmented extranuclear localized 17β-estradiol dendrimer conjugate (EDC)-mediated phosphorylation of Akt (Ser473). These studies suggest distinct subcellular compartments of cell cycle proteins may convey distinct functions.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 18, 2020
- Source ID
- 10.1038/s41389-020-00266-y
Entities
People
- Agnese Di Rocco
- Anthony W Ashton
- Duanwen Shen
- Hallgeir Rui
- Jun Zhao
- Ke Chen
- Mathew C. Casimiro
- Michael P. Lisanti
- Peter A. Mccue
- Richard G Pestell
- Samuel Achilefu
- Timothy G. Pestell
- Xuanmao Jiao
- Yunguang Sun
- Zhiping Li
Organizations
- National Cancer Institute
- National Institutes of Health
- United States Department of Defense
- United States Department of Health and Human Services