A p53-type response element in the GDF15 promoter confers high specificity for p53 activation.
GDF15 is a transcriptional target gene for p53 and its family members, p63 and p73. Its promoter region contains two p53-type response elements, RE1 and RE2, and RE2 confers p53-specific transactivation. RE2 contains several mismatches from the canonical p53 response element (RRRCWWGYYY). Two mismatches in the RRR span and T base of the RE2 core sequence in the most 3' quarter-site are critical for inhibiting the binding affinity to p63 and p73 and corresponding promoter activity. Our results strongly suggest that differential DNA-binding affinities between p53 family member proteins act, at least in part, to confer specific target gene activation.
Osada
Motonobu
M
Department of Otolaryngology, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Park
Hannah Lui
HL
Park
Min Joo
MJ
Liu
Jun-Wei
JW
Wu
Guojun
G
Trink
Barry
B
Sidransky
David
D
D000595:Amino Acid Sequence; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D055436:Growth Differentiation Factor 15; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology*; D020218:Response Elements / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D009687:Nuclear Proteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins