We have previously identified a Rho protein, RhoD, which localizes to the plasma membrane and the early endocytic compartment. Here, we show that a GTPase-deficient mutant of RhoD, RhoDG26V, causes hyperplasia and perturbed differentiation of the epidermis, when targeted to the skin of transgenic mice. In vitro, gain-of-function and loss-of-function approaches revealed that RhoD is involved in the regulation of G1/S-phase progression and causes overduplication of centrosomes. Centriole overduplication assays in aphidicolin-arrested p53-deficient U2OS cells, in which the cell and the centrosome cycles are uncoupled, revealed that the effects of RhoD and its mutants on centrosome duplication and cell cycle are independent. Enhancement of G1/S-phase progression was mediated via Diaph1, a novel effector of RhoD, which we have identified using a two-hybrid screen. These results indicate that RhoD participates in the regulation of cell-cycle progression and centrosome duplication.
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We thank the confocal laser microscope facility of the University of Ioannina for the use of the Leica TCS-SP confocal microscope. We thank George Bartholomatos for FACS analysis; Zoi Lygerou, University of Patras, Greece for critical reading of the manuscript; George Keech for excellent animal husbandry; and Angelika Giner for expert technical assistance. This work was supported by a Research Training Network grant (to MZ and CM) of the European Commission (contract no: HRPN-CT-2000-00081). CM was supported by a short-term EMBO fellowship. MS was supported by the Postgraduate Master’s Program of Biotechnology of the University of Ioannina funded by the Ministry of Education and Religious Affairs of Greece. AK was supported by the PENED 03EΔ688 program, which was co-financed by E.U.-European Social Fund (75%) and the Greek Ministry of Development-GSRT (25%). RGP was supported by grants from the National Health and Medical Research Council of Australia.
The authors declare no conflict of interest.
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Kyrkou, A., Soufi, M., Bahtz, R. et al. RhoD participates in the regulation of cell-cycle progression and centrosome duplication. Oncogene 32, 1831–1842 (2013). https://doi.org/10.1038/onc.2012.195
- centrosome cycle
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