| First Author | Ramadoss S | Year | 2011 |
| Journal | Mol Cell Biol | Volume | 31 |
| Issue | 5 | Pages | 924-34 |
| PubMed ID | 21189284 | Mgi Jnum | J:169184 |
| Mgi Id | MGI:4939985 | Doi | 10.1128/MCB.00576-10 |
| Citation | Ramadoss S, et al. (2011) Transducin {beta}-Like Protein 1 Recruits Nuclear Factor {kappa}B to the Target Gene Promoter for Transcriptional Activation. Mol Cell Biol 31(5):924-34 |
| abstractText | Nuclear factor kappaB (NF-kappaB) signaling controls a wide range of cellular functions such as tumor progression and invasion by inducing gene expression. Upon stimulation, NF-kappaB is translocated to the nucleus and binds to its target gene promoters to activate transcription by recruiting transcription coactivators. Although significant progress has been made in understanding NF-kappaB-mediated transactivation, little is known about how NF-kappaB is recruited to its target gene promoters. Here, we report that transducin beta-like protein 1 (TBL1) controls the expression of NF-kappaB target genes by directly binding with NF-kappaB and facilitating its recruitment to target gene promoters. Tumor necrosis factor alpha stimulation triggered the formation of an NF-kappaB and TBL1 complex and subsequent target gene promoter binding. Knockdown of TBL1 impaired the recruitment of NF-kappaB to its target gene promoters. Interestingly, analysis of the Oncomine database revealed that TBL1 mRNA levels were significantly higher in invasive breast cancer tissues than in breast adenocarcinoma tissue. Consistently, TBL1 knockdown significantly reduced the invasive potential of breast cancer cells by inhibiting NF-kappaB. Our results reveal a new mechanism for the regulation of NF-kappaB activation, with important implications for the development of novel strategies for cancer therapy by targeting NF-kappaB. |
