Regulation Of E2F1 Protein Satbility And Transcription Activity By Histone Deacetylase 11

E2F1 is a very important transcript factor, which has conserved DNA-binding and activation domain. it plays a critical role in early cell cycle progression and apotosis. During the G1 phase, E2F1 participated in the cell cycle from the G1 phase to S phase. Before the cell cycle, an E2F1-Rb complex represses transcription by recruiting histones deacetylase. When cells enter the cell cycle, pRb becomes hyperphorylated and relase free E2F1, then cell pass the S phase.studys suggest that it contains a disruption in the E2F1 regulatory pathway in many human cancers.so E2F1 is a critical facor in cell growth regulation in vivo.When DNA damage, E2F1 transcription activity was enhanced greatly, and can induce apoptosis by p53 dependence pathway or p53 independence pathway.HDAC11 is the newest member of the zinc-dependent family of histone deacetylases.it is a protein which has 347 resiudes with a molecular mass of 39KD. HDAC11 contains conserved residues in the catalytic core region. Many reports indicate that the level of HDAC11 mRNA is low in many human tissues and the high expression level is limited to brain, heart, skeletal muscle, and kidney. But the studys also find that HDAC11 was highly expressed in many human cancer cell lines. It is suggested that HDAC11 may play a very important role in the cell signal pathway. But many studys remained to be done. so far it is reported that the HDACA11 can regulates the expression of interleukinlO in immune cell. they identify HDAC11, as a key immunoregulator by inhibiting IL-10 expression in antigen-presenting cells.here we find that HDAC11 may be also an important regulator of E2F1,which binds to E2F1 and downregulate acetylation level of E2F1. First our datas show that HDAC11 can inbibit the expression of E2F1 in protein level and promote the degradation rate of E2F1. in the futher study, the results suggest that HDAC11 can regulate the acetylaton level and the ubiqution level of E2F1. As we all know, E2F1 can be greatly acetylated by the CBP, and improve the transcription activity of E2F1.here we found that HDAC11 can inhibit the acetylation of E2F1 and inactivity E2F1. so in the study we identify HDAC11,the new member of HDACs family interacts with E2F1 and mediate many activites assosicated with E2F1. It helps the further study to explore the important role in cancer and maybe is a new target to the treatment of cancer.