The p53-targeting human phosphatase hCdc14A interacts with the Cdk1/cyclin B complex and is differentially expressed in human cancers.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Paulsen
Michelle T
MT
Department of Radiation Oncology, Division of Radiation & Cancer Biology, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA. tenbroek@umich.edu
Starks
Adrienne M
AM
Derheimer
Frederick A
FA
Hanasoge
Sheela
S
Li
Liwu
L
Dixon
Jack E
JE
Ljungman
Mats
M
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000096:biosynthesis*; D002460:Cell Line; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000096:biosynthesis*; D003570:Cytidine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D008938:Mitosis; D008954:Models, Biological; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D010766:Phosphorylation; D061988:Proteasome Inhibitors; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases
D019926:Cyclin B; D061988:Proteasome Inhibitors; D003570:Cytidine Triphosphate; C038673:5-aza-2'-deoxycytidine-5'-triphosphate; D016203:CDC2 Protein Kinase; D010744:Phosphoric Monoester Hydrolases; C120902:CDC14A protein, human; D017027:Protein Tyrosine Phosphatases; D001374:Azacitidine