LMO3 interacts with p53 and inhibits its transcriptional activity.
High expression of LMO3 contributes to the development and aggressiveness of neuroblastoma. LMO3 belongs to the LIM-only protein family, in which de-regulation of its members is implicated in human carcinogenesis. However, the molecular mechanism of LMO3 activity in oncogenesis remained poorly characterized. We found that LMO3 is a direct interacting partner of p53 both in vitro and in vivo. The DNA-binding domain of p53 is required for this interaction. Furthermore, expression of LMO3 repressed p53-dependent mRNA expression of its target genes by suppressing promoter activation. Interestingly, chromatin immunoprecipitation assay showed that LMO3 facilitated p53 binding to its response elements. This suggests that LMO3 acts as a co-repressor of p53, suppressing p53-dependent transcriptional regulation without inhibition of its DNA-binding activity.
Larsen
Steven
S
Division of Biochemistry and Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba, Japan.
Yokochi
Tomoki
T
Isogai
Eriko
E
Nakamura
Yohko
Y
Ozaki
Toshinori
T
Nakagawara
Akira
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D060588:LIM Domain Proteins; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C502335:LMO3 protein, human; D015513:Oncogene Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA