Investigating The Mechanistic Role Of RXR? In Mitotic Regulation

The cell cycle or cell-division cycle is the series of events that take place in a cell leading to its division and duplication of its DNA(DNA replication)to produce two daughter cells.Basically,the cell cycle can be divided to the interphase and the cell division.The cell cycle consists of four distinct phases:G1 phase,S phase(synthesis),G2 phase(collectively known as interphase)and M phase(mitosis).M phase is itself composed of two tightly coupled processes:mitosis,in which the cell's chromosomes are divided between the two daughter cells,and mitosis,in which the cell's cytoplasm divides forming distinct cells.During mitosis the spindle apparatus partitions and transports duplicated chromatids into the cytoplasm of the separating daughter cells.The process thereby ensures that chromosome number and complement are maintained from one generation to the next,which is the foundation of the whole life process.The retinoid receptor(RXR?)belongs to the important members of the nuclear receptor superfamily.It plays pivotal roles in various biological processes throughout the whole life,including embryonic formation,organ maturation,metabolism,and so on.However,the function of RXR? in the cell cycle is still a field to be explored.From RXR?'s A region to F region,,previous studies often focus on the DNA binding region(region C)and the ligand binding region(region E)of RXR? a but the understanding of the function of the A/B region is still very limited.The RXR?phosphorylated by CDK1/cyclinBl was observed in previous study,and the phosphorylation disappeared after the A/B region of RXM? was absent;however,the researchers did not continue the study to the phenomenon at that time.In addition,some researchers found that the placental and embryonic development of mice was affected by knocking out of the A/B domain of RXR a.And the malformations and developmental deficiencies of fetal vitamin A deficiency(VAD)syndrome,but the specific molecular mechanisms were not revealed.CDK1 is one of the most important regulators in the cell cycle,whihc is encoded by the cdc2 gene and has a molecular weight of about 34 kd.CDK1 is a serine/threonine protein kinase,which controls two checkpoint in the G1/S and G2/M phase of the cell cycle.The CDK1/cyclinBl complex controls the cell' s entry and exit in mitosis.Our study shows that the CDK1/cyclinB1 complex can interact with RXR? and phosphorylate its 56th and 70 th Serine.And the modified form of RXM? is essential for the mitosis.Experimental results show that overexpression of RXR? can accelerate cell cycle progression.On the other hand,knocking down RXR? causes the slowing down of mitosis,resulting in multinucleated cells.Interestingly,compensating the RXR a-mimic phosphorylated mutants(RXR?-S56/70D)can rescue the abnormal cell cycle,however,RXR a ' s phosphorylation inactivated mutant(RXR?-S56/70D)can exerts no effect on it.In summary,RXR?' s 56th and 70 th Serine in A/B domain are phosphorylated by CDK1,as a result,the modified RXR? regulates the progression of mitosis.This study firstly reveals the RXR?'s regulation function on cell cycle,which enhances the understanding of RXM? A/B domain,and pave a new field for RXR?'s research and the studies of nuclear receptors regulation function in cell cycle.The results is also an important complement to the mechanisms of how CDK1 regulates the cell cycle,and adds a new understanding of the molecular mechanism of understanding the cell cycle.