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

Abstract

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.

CONCLUSION:

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.

• Authors: Michelle T Paulsen, Adrienne M Starks, Frederick A Derheimer, Sheela Hanasoge, Liwu Li, Jack E Dixon, Mats Ljungman
• Journal: Molecular cancer (Mol Cancer) Vol. 5 Pg. 25 (Jun 19 2006) ISSN: 1476-4598 [Electronic] England
• PMID: 16784539 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cyclin B
• Proteasome Inhibitors
• Cytidine Triphosphate
• 5-aza-2'-deoxycytidine-5'-triphosphate
• CDC2 Protein Kinase
• Phosphoric Monoester Hydrolases
• CDC14A protein, human
• Protein Tyrosine Phosphatases
• Azacitidine

Topics

• Azacitidine (analogs & derivatives, pharmacology)
• CDC2 Protein Kinase (biosynthesis)
• Cell Line
• Cell Line, Tumor
• Cyclin B (biosynthesis)
• Cytidine Triphosphate (analogs & derivatives, pharmacology)
• Gene Expression Regulation, Neoplastic
• Genes, p53
• Humans
• Mitosis
• Models, Biological
• Phosphoric Monoester Hydrolases (genetics)
• Phosphorylation
• Proteasome Inhibitors
• Protein Binding
• Protein Tyrosine Phosphatases