CDC25 B与14-3-3相互作用的研究

Interaction of 14-3-3 and CDC25 B

有研究表明在肿瘤发生发展的过程中，癌细胞的有丝分裂失控是肿瘤发生的主要原因。因此，对细胞分裂调控机制的研究成为目前研究的热点。其中细胞分裂周期25 B （ cell division cycle 25 B， CDC25B）和14-3-3是与细胞分裂有着密切关系的调控子。目前研究已经发现PKA／CDC25B／MPF （ CDC2-cyclinB1）和PKA／CDC25B／14-3-3／MPF是调控细胞有丝分裂的两条重要信号转导途径。蛋白激酶A （ pro-tein kinase A， PKA）是一种环磷酸腺苷（ cyclic adenosine monophosphate， cAMP）依赖性蛋白激酶，可以通过磷酸化下游的靶蛋白，抑制靶蛋白正常发挥作用，从而发挥调节作用。实验研究发现， PKA可以通过磷酸化CDC25B某些位点的丝氨酸残基，使CDC25B处于磷酸化状态，不能使成熟促进因子（ maturation pro-moting factor， MPF）的催化亚基细胞分裂周期2蛋白（cell division cycle 2， CDC2）第15位酪氨酸脱磷酸，因而不能激活MPF，使细胞分裂发生阻滞，不能发生G2／M的转化。14-3-3可以通过CDC25B／14-3-3／MPF途径调节有丝分裂，14-3-3通过结合已经发生磷酸化的CDC25 B的氨基酸（丝氨酸或者苏氨酸）残基，阻止CDC25B进入细胞核，从而引起细胞分裂的阻滞畅这样也就提示可以将14-3-3作为靶位点进行靶向治疗，治疗肿瘤疾病。

Research shows that the uncontrolled mitosis of cancer cells is responsible for the formation of a tumor.The regulation mechanism of cell division has become a research focus.CDC25 B and 14-3-3 are regulators that are closely related with cell division.Currently, several studies have found that PKA/CDC25 B/MPF （CDC2-cyclin B1） and PKA/CDC25 B/14-3-3/MPF are two important signal transduction pathways that regulate the mitosis.Protein kinase A （ PKA ） is a cAMP-dependent protein kinase and plays a regulatory role by phosphorylating target proteins located at its downstream and thereby inhibiting their function.Experimental study found that PKA can phos-phorylate the serine residues of certain sites of CDC25 B, resulting in the maintenance of phospho-rylated catalytic subunit CDC2-Tyr15 of MPF and therefore the inactivation of MPF.The G2/M con-version and cell division are consequently arrested.14-3-3 regulates mitosis through CDC25 B/14-3-3/MPF pathways.It combines with amino acid residues （ serine or threonine ） of phosphorylated CDC25 B to prevent CDC25 B transfer into the nucleus, and inhibit cell division.It is suggested that 14-3-3 can be as a target site for treatment of neoplastic diseases.