title: The impact of R213 mutation on p53-mediated p21 activity.
abstract: p53 is a transcriptional regulator in the nucleus that functions as a tumor suppressor and its mutations are frequently found in human tumors. It has been reported that p53 with R213Q mutation is exist in certain tumor cell lines and its methylation on R213 as well. However, the mechanisms and consequences of these modifications on p53 function are not fully understood. Mutations of p53 at R213Q (R/Q) and R213K (R/K) were respectively constructed and transfected into the p53 null H1299 cells. As shown in luciferase reporter assays, either R/Q or R/K disrupted the efficiency of p53 transactivation. EMSA and ChIP assays revealed that these mutants were less efficient in targeting the consensus binding sequences of p53 in the regulatory region of p21 gene. In addition, R/Q and R/K mutants attenuated the expression of p21 gene and counteracted the p53 mediated G1/S arrest to deliver a normal cell cycle progression as in the mock H1299 cells. Through this study, we have provided the first evidence on the pivotal role of arginine 213 that determines the p53 mediated functions of p21 in human cancer cells.
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, 5 Dongdan Santiao, Beijing 100005, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, 5 Dongdan Santiao, Beijing 100005, China.
authors.forename: Yan-jun
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, 5 Dongdan Santiao, Beijing 100005, China.
authors.forename: Hai-yong
authors.initials: HY
authors.lastname: Zhao
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, 5 Dongdan Santiao, Beijing 100005, China.
authors.forename: Qiao-li
authors.initials: QL
authors.lastname: Zhai
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, 5 Dongdan Santiao, Beijing 100005, China. Electronic address: yezhang@pumc.edu.cn.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, 5 Dongdan Santiao, Beijing 100005, China. Electronic address: yfshen@imicams.ac.cn.
authors.forename: Yu-fei
authors.initials: YF
authors.lastname: Shen
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D020125:Mutation, Missense; D011485:Protein Binding; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Arginine; Mutation; p21; p53