Transcriptional upregulation of restin by p53.
Restin, belonging to the melanoma-associated antigen superfamily, was firstly cloned from the differentiated HL-60 cells when induced by all-trans retinoic acid (ATRA) in our lab. Our previous results showed that restin might be correlated to cell cycle arrest. Due to the importance of p53 in the regulation of cell growth and the relationship between p53 and ATRA, we tried to test the relationship between p53 and restin. Firstly, transfection results showed that p53 was able to upregulate the expression of restin at the transcriptional level when p53 was transfected into eukaryotic cells. Secondly, the bioinformatics analysis revealed that the upstream sequence (about 2 kb) from the first ATG of the ORF of restin gene contained a p53 binding site. In order to confirm that p53 was involved in the transcriptional regulation of restin, we cloned the upstream sequence of restin and constructed the promoter luciferase reporter system. From the luciferase activity, we demonstrated that the promoter of restin gene could be induced by ATRA. Then, another two luciferase reporter plasmids driven by the reporter of restin with no (RPdelta p53-luc) or mutant (mRP-luc) p53 binding site were constructed to see the regulation of restin by p53. Results showed that the transcriptional upregulation of restin gene was not due to the putative p53 binding site on the upstream of restin gene. We proposed that p53 upregulated restin transcription through an indirect way rather than direct interaction with the cis-activating element of the restin promoter.
Wang
RuiHua
R
State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, China.
Lu
Fan
F
Fu
HaiYan
H
Wu
YouSheng
Y
Yang
GuoDong
G
Zhao
WenMing
W
Zhao
ZhongLiang
Z
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics*
D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C076744:cytoplasmic linker protein 170