Department of Surgical and Radiological Sciences, School of Veterinary Medicine
Department of Internal Medicine, School of Medicine
The Biochemical and Biological Functions of the p53 Family of Tumor Suppressors
The p53 family proteins are transcription factors and consist of p53, p63, and p73. Each member regulates a diverse array of both common and unique target genes. These target genes mediate various activities for the p53 family proteins, including the cell cycle control, apoptosis, differentiation, senescence, DNA repair, normal development and tumor suppression. p53 is a tumor suppressor and found to be mutated or inactivated in greater than 60% of all human cancers. Mutant p53 is not only defective in tumor suppression but also promotes tumor formation. However, p63 and p73 appear to be necessary for the development of various tissues and immune response in addition to tumor suppression. To address these diverse activities for the p53 family proteins, we focus on the following areas of research:
(1) to determine the mechanism by which the p53 family proteins differentially regulate gene expression
(2) to determine how p53 family target genes mediate the diverse functions of p53 family proteins in tumor suppression, normal development, and senescence
(3) to determine the mechanism by which mutant p53 obtains a gain of function in promoting tumor formation
(4) to determine the mechanism by which the expression and activity for each p53 family protein is regulated
(5) to develop a dog model to study the p53 family proteins in tumor suppression.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
- Tupper 2117-2119
- Y. Zhang, PhD; J. Zhang, PhD; Chris Lucchesi, PhD; S. Mohibi, PhD
Honors and Awards
- Distinguished Teaching Award, Medical College of Georgia, 2000
- Pfizer Distinguished Research Award, School of Veterinary Medicine, University of California at Davis, 2010
- Elected Fellow, American Association for the Advancement of Science, 2015
- Member of the Editorial Board, Journal of Biological Chemistry, 2007-2012
- Member of the Editorial Board, Cancer Biology and Therapy, 2006-2009
- American Association for Cancer Research
- American Society of Biochemistry and Molecular Biology
- American Association for Microbiology
- 1991 PhD Microbiology Michigan State University
- 1985 MS Infectious Diseases Nanjing Agricultural University in China
- 1982 BVSc Veterinary Medicine Anhui Agricultural University in China
(Selected from ~152 publications)
Zhang J, Xu E, Ren E, Yan W, Zhang M, Chen M, Cardiff RD, Imai DM, Wisner E, Chen X. 2014. Mice Deficient in RBM38, a RNA Binding Protein and a Target of the p53 Family, are Susceptible to Accelerated Aging and Spontaneous Tumors. Proc Natl Acad Sci. 2014 Dec 30;111(52):18637-42. PMC4284600.
Yan W, Scoumanne A, Jung YS, Xu E, Zhang J, Zhang Y, Ren C, Sun P, Chen X. 2016.Mice deficient in poly(C)-binding protein 4 are susceptible to spontaneous tumors through increased expression of ZFP871 that targets p53 for degradation.Genes Dev. 30(5): 522-534. PMC4782047.
Zhang Y, Qian Y, Zhang J, Yan W, Jung YS, Chen M, Huang E, Lloyd K, Duan Y, Wang J, Liu G, Chen X. 2017. Ferredoxin reductase is critical for p53-dependent tumor suppression via iron regulatory protein 2. Genes Dev. 31(12):1243-1256. PMC5558926.
Yang HJ, Zhang J, Yan W, Cho SJ, Scoumanne A, Lucchesi C, Chen M, Huang EC, Chen X. 2017. Ninjurin 1 has two opposing functions in tumorigenesis in a p53-dependent manner.Proc Natl Acad Sci U S A. 114(43):11500-11505. PMCID: PMC5664541.