RhoD participates in the regulation of cell-cycle progression and centrosome duplication.
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.
Laboratory of Biological Chemistry, University of Ioannina Medical School, Ioannina, Greece.
A
A
Kyrkou
M
M
Soufi
R
R
Bahtz
C
C
Ferguson
M
M
Bai
R G
RG
Parton
I
I
Hoffmann
M
M
Zerial
T
T
Fotsis
C
C
Murphy
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018385:Centrosome / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D000080865:Formins; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase / Q000502:physiology*; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics; D020798:Two-Hybrid System Techniques; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C108962:DIAPH1 protein, human; D000080865:Formins; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C105243:RHOD protein, human; D020741:rho GTP-Binding Proteins