The Human Cdc14 Phosphatases Interact with and Dephosphorylate the Tumor Suppressor Protein p53*
- From the ‡Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157 and the Departments of ‖Biological Chemistry and ¶Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0606
Abstract
The yeast Cdc14 phosphatase has been shown to play an important role in cell cycle regulation by dephosphorylating proteins phosphorylated by the cyclin-dependent kinase Cdc28/clb. We recently cloned two human orthologs of the yeastCDC14, termed hCDC14A and -B, the gene products of which share ∼80% amino acid sequence identity within their N termini and phosphatase domains. Here we report that the hCdc14A and hCdc14B proteins interact with the tumor suppressor protein p53 both in vitro and in vivo. This interaction is dependent on the N termini of the hCdc14 proteins and the C terminus of p53. Furthermore, the hCdc14 phosphatases were found to dephosphorylate p53 specifically at the p34Cdc2/clb phosphorylation site (p53-phosphor-Ser315). Our findings that hCdc14 is a cyclin-dependent kinase substrate phosphatase suggest that it may play a role in cell cycle control in human cells. Furthermore, the identification of p53 as a substrate for hCdc14 indicates that hCdc14 may regulate the function of p53.
Footnotes
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↵* This work was supported by Cancer Biology Training Program National Institutes of Health Grant CA09676 (to L. L.) and by the Walther Cancer Institute (to J. E. D.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵§ To whom correspondence should be addressed. Tel.: 336-716-6040; Fax: 336-716-3825; E-mail: lwli@wfubmc.edu.
- Abbreviations:
- ORF
-
open reading frame
- PCR
-
polymerase chain reaction
- GST
-
glutathioneS-transferase
- X-gal
-
5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside
- PAGE
-
polyacrylamide gel electrophoresis
- GFP
-
green fluorescent protein
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- Received October 26, 1999.
- Revision received December 2, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
