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Molecular and Cellular Biology, August 2005, p. 6509-6520, Vol. 25, No. 15
0270-7306/05/$08.00+0 doi:10.1128/MCB.25.15.6509-6520.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Regulation of p53-MDMX Interaction by Casein Kinase 1 Alpha
Lihong Chen,
Changgong Li,
Yu Pan, and
Jiandong Chen*
Molecular Oncology Program, H. Lee Moffitt Comprehensive Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612
Received 5 April 2005/
Accepted 4 May 2005
MDMX is a homolog of MDM2 that is critical for regulating p53 function during mouse development. MDMX degradation is regulated by MDM2-mediated ubiquitination. Whether there are other mechanisms of MDMX regulation is largely unknown. We found that MDMX binds to the casein kinase 1 alpha isoform (CK1
) and is phosphorylated by CK1
. Expression of CK1
stimulates the ability of MDMX to bind to p53 and inhibit p53 transcriptional function. Regulation of MDMX-p53 interaction requires CK1
binding to the central region of MDMX and phosphorylation of MDMX on serine 289. Inhibition of CK1
expression by isoform-specific small interfering RNA (siRNA) activates p53 and further enhances p53 activity after ionizing irradiation. CK1
siRNA also cooperates with DNA damage to induce apoptosis. These results suggest that CK1
is a functionally relevant MDMX-binding protein and plays an important role in regulating p53 activity in the absence or presence of stress.
* Corresponding author. Mailing address: H. Lee Moffitt Cancer Center, MRC3057A, 12902 Magnolia Drive, Tampa, FL 33612. Phone: (813) 903-6822. Fax: (813) 903-6817. E-mail:
jchen{at}moffitt.usf.edu.
Molecular and Cellular Biology, August 2005, p. 6509-6520, Vol. 25, No. 15
0022-538X/05/$08.00+0 doi:10.1128/MCB.25.15.6509-6520.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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