These authors contributed equally to this work.
Translokin (Cep57) Interacts with Cyclin D1 and Prevents Its Nuclear Accumulation in Quiescent Fibroblasts
Article first published online: 15 MAR 2011
© 2011 John Wiley & Sons A/S
Volume 12, Issue 5, pages 549–562, May 2011
How to Cite
Ruiz-Miró, M., Colomina, N., Fernández, R. M.H., Garí, E., Gallego, C. and Aldea, M. (2011), Translokin (Cep57) Interacts with Cyclin D1 and Prevents Its Nuclear Accumulation in Quiescent Fibroblasts. Traffic, 12: 549–562. doi: 10.1111/j.1600-0854.2011.01176.x
- Issue published online: 6 APR 2011
- Article first published online: 15 MAR 2011
- Accepted manuscript online: 9 FEB 2011 12:04PM EST
- Received 5 October 2010, revised and accepted for publication 8 February 2011, uncorrected manuscript published online 9 February 2011, published online 15 March 2011
- cell cycle;
- cell proliferation;
- cell quiescence;
- cyclin D1;
Nuclear accumulation of cyclin D1 because of altered trafficking or degradation is thought to contribute directly to neoplastic transformation and growth. Mechanisms of cyclin D1 localization in S phase have been studied in detail, but its control during exit from the cell cycle and quiescence is poorly understood. Here we report that translokin (Tlk), a microtubule-associated protein also termed Cep57, interacts with cyclin D1 and controls its nucleocytoplasmic distribution in quiescent cells. Tlk binds to regions of cyclin D1 also involved in binding to cyclin-dependent kinase 4 (Cdk4), and a fraction of cyclin D1 associates to the juxtanuclear Tlk network in the cell. Downregulation of Tlk levels results in undue nuclear accumulation of cyclin D1 and increased Cdk4-dependent phosphorylation of pRB under quiescence conditions. In turn, overexpression of Tlk prevents proper cyclin D1 accumulation in the nucleus of proliferating cells in an interaction-dependent manner, inhibits Cdk4-dependent phosphorylation of pRB and hinders cell cycle progression to S phase. We propose that the Tlk acts as a key negative regulator in the pathway that drives nuclear import of cyclin D1, thus contributing to prevent pRB inactivation and to maintain cellular quiescence.