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The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53
1Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. lwli@wfubmc.edu
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 yeast CDC14, termed hCDC14A and -B, the gene products of which share approximately 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 p34(Cdc2)/clb phosphorylation site (p53-phosphor-Ser(315)). 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.
Insights
Human Cdc14A and Cdc14B phosphatases interact with and dephosphorylate the tumor suppressor p53. This suggests a role for hCdc14 in regulating p53 function and human cell cycle control.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Yeast Cdc14 phosphatase regulates cell cycle by dephosphorylating proteins targeted by cyclin-dependent kinase Cdc28/clb.
- Two human orthologs, hCDC14A and hCDC14B, were identified, sharing significant sequence identity with yeast Cdc14.
Purpose of the Study:
- To investigate the interaction between human Cdc14A/B proteins and the tumor suppressor p53.
- To determine if hCdc14 proteins can dephosphorylate p53 and identify specific phosphorylation sites.
Main Methods:
- In vitro and in vivo interaction assays to study hCdc14 and p53 binding.
- Biochemical assays to analyze p53 dephosphorylation by hCdc14 at specific sites.
Main Results:
- hCdc14A and hCdc14B proteins were found to interact with p53 both in vitro and in vivo.
- The interaction depends on the N termini of hCdc14 and the C terminus of p53.
- hCdc14 phosphatases dephosphorylate p53 at the p34(Cdc2)/clb phosphorylation site (p53-phosphor-Ser(315)).
Conclusions:
- hCdc14 functions as a cyclin-dependent kinase substrate phosphatase, suggesting a role in human cell cycle control.
- The identification of p53 as a substrate indicates that hCdc14 may regulate p53 function.