Regulation of cell proliferation by ERK and signal-dependent nuclear translocation of ERK is dependent on Tm5NM1-containing actin filaments
- Author(s)
- Schevzov, G; Kee, AJ; Wang, B; Sequeira, VB; Hook, J; Coombes, JD; Lucas, CA; Stehn, JR; Musgrove, EA; Cretu, A; Assoian, R; Fath, T; Hanoch, T; Seger, R; Pleines, I; Kile, BT; Hardeman, EC; Gunning, PW;
- Details
- Publication Year 2015-07-01,Volume 26,Issue #13,Page 2475-90
- Journal Title
- Mol Biol Cell
- Publication Type
- Journal Article
- Abstract
- ERK regulated cell proliferation requires multiple phosphorylation events catalysed first by MEK and then Casein Kinase 2 (CK2) followed by interaction with importin7 and subsequent nuclear translocation of pERK. We report that genetic manipulation of a core component of the actin filaments of cancer cells, the tropomyosin Tm5NM1, regulates the proliferation of normal cells both in vitro and in vivo. Mouse embryo fibroblasts (MEFs) lacking Tm5NM1, which have reduced proliferative capacity, are insensitive to inhibition of ERK by peptide and small molecule inhibitors indicating that ERK is unable to regulate proliferation of these knockout (KO) cells. Treatment of wild type MEFs with a CK2 inhibitor to block phosphorylation of the nuclear translocation signal in pERK resulted in greatly decreased cell proliferation and a significant reduction in the nuclear translocation of pERK. In contrast, Tm5NM1 KO MEFs which show reduced nuclear translocation of pERK were unaffected by inhibition of CK2. This suggested that it is nuclear translocation of CK2-phosphorylated pERK which regulates cell proliferation and this capacity is absent in Tm5NM1 KO cells. Proximity ligation assays confirmed a growth factor-stimulated interaction of pERK with Tm5NM1 and that the interaction of pERK with importin7 is greatly reduced in the Tm5NM1 KO cells.
- Publisher
- ASCB
- Research Division(s)
- Chemical Biology
- PubMed ID
- 25971798
- Publisher's Version
- https://doi.org/10.1091/mbc.E14-10-1453
- NHMRC Grants
- NHMRC/1016647,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-05-22 11:19:39
Last Modified: 2016-04-20 12:17:14