Genetic characterization of p27Kip1 and stathmin role in controlling cell proliferation in vivo

ABSTRACT: The CDK inhibitor p27Kip1 is a critical regulator of cell cycle progression, but the mechanisms by which p27Kip1 controls cell proliferation in vivo are still not fully elucidated. We recently demonstrated that the microtubule destabilizing protein stathmin is a relevant p27Kip1binding partner involved in the regulation of cell motility. To get more insights into the in vivo significance of this interaction, we generated p27Kip1 and stathmin double knock out (DKO) mice. Interestingly, thorough characterization of DKO mice demonstrated that most of the phenotypes of p27Kip1 null mice linked to the hyperproliferative behavior, such as the increased body and organ weights, the outgrowth of the retina basal layer and the development of pituitary adenomas, were reverted by co-ablation of stathmin. In vivo analyses showed a reduced proliferation rate in DKO compared to p27kip1 null mice, linked, at molecular level, to decreased kinase activity of CDK4/6, rather than of CDK1 and CDK2. Gene expression profile analyses of mouse thymuses confirmed the phenotypes observed in vivo, demonstrating that DKO clustered with WT and not with p27KO thymuses. Taken together, the results demonstrate that stathmin cooperates with p27Kip1 to control the early phase of G1 to S phase transition and strongly suggest that this function has particular relevance in the contest of tumor progression. Four-conditions experiment (four different mouse genotypes), 6 biological replicates of wild type mouse thymus, 6 biological replicates of p27 knock-out mouse thymus, 6 biological replicates of stathmin knock-out mouse thymus, 6 biological replicates of double knock-out (p27 and stathmin) mouse thymus. Reference design: pool of RNAs derived from mouse fibroblasts of all the genotypes.Reference design;

ORGANISM(S): Mus musculus

SUBMITTER: daniela marconi 

PROVIDER: E-GEOD-60078 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress