The p53-targeting human phosphatase hCdc14A interacts with the Cdk1/cyclin B complex and is differentially expressed in human cancers.
The p53-targeting human phosphatase hCdc14A interacts with the Cdk1/cyclin B complex and is differentially expressed in human cancers.
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DOI：
10.1186/1476-4598-5-25
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发表时间：
2006-06-19
期刊：
影响因子：
37.3
通讯作者：
Ljungman M
中科院分区：
文献类型：
--
作者：
Paulsen MT;Starks AM;Derheimer FA;Hanasoge S;Li L;Dixon JE;Ljungman M
进化上保守的细胞周期蛋白依赖性激酶磷酸酶hCdc 14 A已被证明在有丝分裂退出和中心体复制周期的调节中发挥潜在的作用。我们最近发现hCdc 14 A在体外和体内都能与肿瘤抑制因子p53相互作用，并在体外特异性地使p53的ser 315位点去磷酸化。在这项研究中，我们开发了针对hCdc 14 A的抗体，以研究hCdc 14 A在人体组织和癌细胞中的表达和调控。我们发现，hCdc 14 A在人体组织中的差异表达，并在75个癌细胞系检查。用组蛋白去乙酰化酶抑制剂TSA、去甲基化剂5-氮杂-2 '-脱氧胞苷或蛋白酶体抑制剂MG 132处理显著诱导表达低水平或检测不到水平hCdc 14 A的细胞系中hCdc 14 A的表达。在携带野生型p53的癌细胞系中hCdc 14 A的低表达存在强烈的偏倚，表明高Cdc 14 A表达与野生型p53表达不相容。我们目前的证据表明，hCdc 14 A在体内p53的ser 315位点的去磷酸化的作用，hCdc 14 A形成一个复合物与Cdk 1/细胞周期蛋白B在间期，但不是在有丝分裂。我们的研究结果表明，hCdc 14 A在人类癌细胞中的差异表达，hCdc 14 A可以与p53和Cdk 1/cyclin B复合物相互作用，可能暗示hCdc 14 A表达失调可能在癌变过程中发挥作用。
The evolutionary conserved cyclin-dependent kinase phosphatase hCdc14A has been shown to play potential roles in the regulation of mitotic exit and in the centrosome duplication cycle. We have recently shown that hCdc14A also can interact with the tumor suppressor p53 both in vitro and in vivo and specifically dephosphorylates the ser315 site of p53 in vitro. In this study we developed antibodies against hCdc14A to investigate the expression and regulation of hCdc14A in human tissues and cancer cells. We show that hCdc14A is differentially expressed in human tissues and in 75 cancer cell lines examined. Treatments with the histone deacetylase inhibitor TSA, the demethylating agent 5-aza-2'-deoxycytodine or the proteasome inhibitor MG132 significantly induced expression of hCdc14A in cell lines expressing low or undetectable levels of hCdc14A. There was a strong bias for low expression of hCdc14A in cancer cell lines harboring wild-type p53, suggesting that high Cdc14A expression is not compatible with wild-type p53 expression. We present evidence for a role for hCdc14A in the dephosphorylation of the ser315 site of p53 in vivo and that hCdc14A forms a complex with Cdk1/cyclin B during interphase but not during mitosis. Our results that hCdc14A is differentially expressed in human cancer cells and that hCdc14A can interact with both p53 and the Cdk1/cyclin B complex may implicate that dysregulation of hCdc14A expression may play a role in carcinogenesis.
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DOI：
10.1083/jcb.200202054
发表时间：
2002-09-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gruneberg U;Glotzer M;Gartner A;Nigg EA
通讯作者：
Nigg EA
影响因子：
4.8
作者：
Bembenek, J;Yu, HT
通讯作者：
Yu, HT
影响因子：
4
作者：
Mishra, M;Karagiannis, J;Balasubramanian, MK
通讯作者：
Balasubramanian, MK
影响因子：
9.2
作者：
Oliferenko, S;Balasubramanian, MK
通讯作者：
Balasubramanian, MK
影响因子：
21.3
作者：
Mailand, N;Lukas, C;Lukas, J
通讯作者：
Lukas, J