| First Author | Wang J | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 37 | Pages | 16131-6 |
| PubMed ID | 20805509 | Mgi Jnum | J:164358 |
| Mgi Id | MGI:4833715 | Doi | 10.1073/pnas.1002603107 |
| Citation | Wang J, et al. (2010) CCAAT/enhancer binding protein delta (C/EBPdelta, CEBPD)-mediated nuclear import of FANCD2 by IPO4 augments cellular response to DNA damage. Proc Natl Acad Sci U S A 107(37):16131-6 |
| abstractText | Maintenance of genomic integrity is an essential cellular function. We previously reported that the transcription factor and tumor suppressor CCAAT/enhancer binding protein delta (C/EBPdelta, CEBPD; also known as 'NFIL-6beta') promotes genomic stability. However, the molecular mechanism was not known. Here, we show that C/EBPdelta is a DNA damage-induced gene, which supports survival of mouse bone marrow cells, mouse embryo fibroblasts (MEF), human fibroblasts, and breast tumor cells in response to the DNA cross-linking agent mitomycin C (MMC). Using gene knockout, protein depletion, and overexpression studies, we found that C/EBPdelta promotes monoubiquitination of the Fanconi anemia complementation group D2 protein (FANCD2), which is necessary for its function in replication-associated DNA repair. C/EBPdelta interacts with FANCD2 and importin 4 (IPO4, also known as 'Imp4' and 'RanBP4') via separate domains, mediating FANCD2-IPO4 association and augmenting nuclear import of FANCD2, a prerequisite for its monoubiquitination. This study identifies a transcription-independent activity of C/EBPdelta in the DNA damage response that may in part underlie its tumor suppressor function. Furthermore, we report a function of IPO4 and nuclear import in the Fanconi anemia pathway of DNA repair. |
