Format

Send to

Choose Destination

RETRACTED ARTICLE

See: Retraction Notice

Cancer Res. 2010 Jul 1;70(13):5379-88. doi: 10.1158/0008-5472.CAN-09-4199. Epub 2010 Jun 8.

High-mobility group A1 proteins regulate p53-mediated transcription of Bcl-2 gene.

Author information

1
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Università degli Studi di Napoli Federico II, Naples, Italy.

Abstract

We have previously described a mechanism through which the high-mobility group A1 (HMGA1) proteins inhibit p53-mediated apoptosis by delocalizing the p53 proapoptotic activator homeodomain-interacting protein kinase 2 from the nucleus to the cytoplasm. By this mechanism, HMGA1 modulates the transcription of p53 target genes such as Mdm2, p21(waf1), and Bax, inhibiting apoptosis. Here, we report that HMGA1 antagonizes the p53-mediated transcriptional repression of another apoptosis-related gene, Bcl-2, suggesting a novel mechanism by which HMGA1 counteracts apoptosis. Moreover, HMGA1 overexpression promotes the reduction of Brn-3a binding to the Bcl-2 promoter, thereby blocking the Brn-3a corepressor function on Bcl-2 expression following p53 activation. Consistently, a significant direct correlation between HMGA1 and Bcl-2 overexpression has been observed in human breast carcinomas harboring wild-type p53. Therefore, this study suggests a novel mechanism, based on Bcl-2 induction, by which HMGA1 overexpression contributes to the escape from apoptosis leading to neoplastic transformation.

PMID:
20530667
DOI:
10.1158/0008-5472.CAN-09-4199
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center