The roles of p53R2 in cancer progression based on the new function of mutant p53 and cytoplasmic p21.
Although the deregulated expression of p53R2, a p53-inducible protein and homologue of the R2 subunit of ribonucleotide reductase, has been detected in several human cancers, p53R2 roles in cancer progression and malignancy still remains controversial. In this article, we present a viable hypothesis about the roles of p53R2 in cancer progression and therapy resistance based on the roles of cytoplasmic p21 and mutant p53. Since p53R2 can up-regulate p21 and p21, it in turn has a dual role in cell cycle. Hence, p53R2 can play a dual role in cell cycle progression. In addition, because p53 is the main regulator of p53R2, the mutant p53 may induce the expression of p53R2 in some cancer cells based on the "keep of function" phenomenon. Therefore, depending on the locations of p21 and the new abilities of mutant p53, p53R2 has dual role in cell cycle progression. Since the DNA damaging therapies induce p53R2 expression through the induction of p53, p53R2 can be the main therapy resistance mediator in cancers with cytoplasmic p21.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Bahman
B
Yousefi
Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran.
Mohammad
M
Rahmati
Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran. Electronic address: ahmadi.bchemistry@yahoo.com.
Yasin
Y
Ahmadi
D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000503:physiopathology; D012264:Ribonucleotide Reductases / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; C405947:RRM2B protein, human; D012264:Ribonucleotide Reductases
Cancer progression; Cell cycle; Keep of function phenomenon; Therapy resistance