DEC1 Up-regulates the Stability of Cyclin E by inhibiting its ubiquitination

Overexpression of cyclin E associates with multi-tumorigenesis,including breast,colon,bladder,skin,lung cancer and so on.It is noteworthy that cyclin E can be a prognostic marker in breast cancer.Differentiated embryo-chondrocyte expressed gene 1 (DEC1,also called BHLHE40,BHLHB2,Stra13,or Sharp2) and its related protein DEC2,are members of the basic helix-loop-helix (bHLH) family proteins which are involved in multi-cell progressions,such as cellular differentiation,proliferation,or apoptosis in various tumor cells.In our research,we found that DEC1 up-regulated the protein level of cyclin E in a dose-dependent manner and markedly extended the half-life of cyclin E in breast cancer cell,MCF-7.However,the level of cyclin E has no significant change in DEC 1 overexpressed cells with treatment of MG132 (ubiquitin-proteasome inhibitor),suggesting that DEC 1 may regulate cyclin E protein stability through ubiquitin-proteasome pathway.Next,co-immunoprecipitation experiment showed that DEC 1 significantly repressed the ubiquitination of cyclin E and the interaction between cyclin E and its ubiquitin E3 ligase Fbw7.Therefore,DEC 1 stabilized cyclin E by blocking cyclin E proteasome pathway.At the same time,overexpression of Cyclin E resulted in the decrease in the percentage of G 1 phase cells.Thus,the study on the stability of Cyclin E will contribute to elucidating the molecular mechanism of the generation and development of breast cancer.