First published November 1, 2013 - More info
High-mobility group A1 (HMGA1) overexpression and gene rearrangement are frequent events in human cancer, but the molecular basis of HMGA1 oncogenic activity remains unclear. Here we describe a mechanism through which HMGA1 inhibits p53-mediated apoptosis by counteracting the p53 proapoptotic activator homeodomain-interacting protein kinase 2 (HIPK2). We found that HMGA1 overexpression promoted HIPK2 relocalization in the cytoplasm and inhibition of p53 apoptotic function, while HIPK2 overexpression reestablished HIPK2 nuclear localization and sensitivity to apoptosis. HIPK2 depletion by RNA interference suppressed the antiapoptotic effect of HMGA1, which indicates that HIPK2 is the target required for HMGA1 to repress the apoptotic activity of p53. Consistent with this process, a strong correlation among HMGA1 overexpression, HIPK2 cytoplasmic localization, and low spontaneous apoptosis index (comparable to that observed in mutant p53–carrying tumors) was observed in WT p53–expressing human breast carcinomas. Hence, cytoplasmic relocalization of HIPK2 induced by HMGA1 overexpression is a mechanism of inactivation of p53 apoptotic function that we believe to be novel.
Giovanna Maria Pierantoni, Cinzia Rinaldo, Marcella Mottolese, Anna Di Benedetto, Francesco Esposito, Silvia Soddu, Alfredo Fusco
Original citation: J. Clin. Invest. 2007;117(3):693–702. doi:10.1172/JCI29852.
Citation for this retraction: J. Clin. Invest. 2013;123(11):4979. doi:10.1172/JCI73730.
It has come to our attention that multiple HMGA1 bands in the immunoblot images of Figure 1, A, B, and D, and Figure 3D have been inappropriately duplicated. In addition, the p53 blots in Figure 1, A and B, appear to represent a darker exposure of the same blot. The authors are unable to provide the original source files that were used to generate these data. While the authors maintain that these findings were confirmed in replicate experiments, the JCI Editorial Board has decided to retract this paper due to the evident manipulation in these figure panels. No issues have been raised in regard to any of the other data in this manuscript.
The authors regret the errors and concur with this course of action.