Journal Article
Proceedings of the National Academy of Sciences, vol. 113, iss. 30, pp. 8466-8471, 2016
Authors
Celestino Velásquez, Erdong Cheng, Masahiro Shuda, Paula J. Lee-Oesterreich, Lisa Pogge von Strandmann, Marina A. Gritsenko, Jon M. Jacobs, Patrick S. Moore, Yuan Chang
Abstract
Significance
Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) hyperphosphorylation is implicated in various cancers. Mammalian target of rapamycin (mTOR) targeting of canonical sites—Thr37, Thr46, Ser65, and Thr70—inhibits 4E-BP1 translation repression activity and promotes protein synthesis, which in turn leads to overexpression of several cellular oncoproteins. In addition to the canonical sites, cyclin-dependent kinase 1 (CDK1) phosphorylates 4E-BP1 at Ser83 during mitosis, which interestingly does not affect translation. Rather, this phosphorylation site is permissive for Merkel cell polyomavirus small T viral oncoprotein-induced cell transformation. These findings shed light on a previously unidentified role for mitotic 4E-BP1 in cancer cell growth.
