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 chara...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2010-02, Vol.392 (3), p.252-257
Main Authors: Larsen, Steven, Yokochi, Tomoki, Isogai, Eriko, Nakamura, Yohko, Ozaki, Toshinori, Nakagawara, Akira
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Animals
Cell Line
Cell Line, Tumor
DNA - metabolism
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Humans
LIM Domain Proteins
LIM-only protein
LMO3
Neoplasms - genetics
Neoplasms - metabolism
Neuroblastoma
Oncogene
Oncogene Proteins - genetics
Oncogene Proteins - metabolism
p53
Promoter Regions, Genetic
Protein Structure, Tertiary
Repressor Proteins - genetics
Repressor Proteins - metabolism
Transcription, Genetic
Tumor suppressor
Tumor Suppressor Protein p53 - antagonists & inhibitors
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2009.12.010