| First Author | Ghosh A | Year | 2012 |
| Journal | Nat Cell Biol | Volume | 14 |
| Issue | 12 | Pages | 1270-81 |
| PubMed ID | 23159929 | Mgi Jnum | J:195250 |
| Mgi Id | MGI:5476908 | Doi | 10.1038/ncb2621 |
| Citation | Ghosh A, et al. (2012) Telomerase directly regulates NF-kappaB-dependent transcription. Nat Cell Biol 14(12):1270-81 |
| abstractText | Although elongation of telomeres is thought to be the prime function of reactivated telomerase in cancers, this activity alone does not account for all of the properties that telomerase reactivation attributes to human cancer cells. Here, we uncover a link between telomerase and NF-kappaB, a master regulator of inflammation. We observe that while blocking NF-kappaB signalling can inhibit effects of telomerase overexpression on processes relevant to transformation, increasing NF-kappaB activity can functionally substitute for reduced telomerase activity. Telomerase directly regulates NF-kappaB-dependent gene expression by binding to the NF-kappaB p65 subunit and recruitment to a subset of NF-kappaB promoters such as those of IL-6 and TNF-alpha, cytokines that are critical for inflammation and cancer progression. As NF-kappaB can transcriptionally upregulate telomerase levels, our findings suggest that a feed-forward regulation between them could be the key mechanistic basis for the coexistence of chronic inflammation and sustained telomerase activity in human cancers. |
