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Cell Growth & Differentiation Vol. 12, 175-186, April 2001
© 2001 American Association for Cancer Research

Control of p53 Ubiquitination and Nuclear Export by MDM2 and ARF1

Yanping Zhang and Yue Xiong2

Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [Y. Z.], and Lineberger Comprehensive Cancer Center and Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295 [Y. X.]

p53 and ARF-INK4a are the two most frequently altered loci in human tumors. The activity of p53 protein is inhibited during normal cell growth by the proto-oncoprotein MDM2 through either repression of p53-mediated transcription in the nucleus or proteasomal degradation of p53 protein in the cytoplasm. Responding to oncogenic signal-activated cell hyperproliferation, ARF-mediated antagonism of MDM2 inhibition results in p53 becoming active and its protein levels rising. The biochemical mechanisms of ubiquitination and nuclear export that underlie the functions of ARF and MDM2 in p53 control continue to emerge.




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