Transcriptomics

Dataset Information

0

The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia


ABSTRACT: The NF-κB pathway is a critical regulator of the immune system and has been implicated in cellular transformation and tumorigenesis. NF-κB response is regulated by the activation state of the IκB kinase (IKK) complex and triggered by a wide spectrum of stimuli. We previously reported that NF-κB is downstream of Notch1 in T cell acute lymphoblastic leukaemia (T-ALL), however both the mechanisms involving Notch1-induced NF-κB activation and the potential importance of NF-κB in the maintenance of the disease are unknown. Here we visualize Notch-induced NF-κB activation using both human T-ALL cell lines and animal models of this type of leukemia. We show that it is not Notch1 itself but Hes1, a canonical Notch target, the responsible for sustaining IKK activation in T-ALL. Hes1 exerts its effects by a direct transcriptional repression of the deubiquitinating enzyme CYLD, a well-characterized IKK inhibitor. Consistently, CYLD expression is significantly reduced in primary T-ALL leukemias. Finally, we demonstrate that IKK complex inhibition is a promising option for the targeted therapy of T-ALL as suppression of IKK function affected both the survival of human T-ALL cells in vitro and the maintenance of the disease in vivo. Transcriptional consequences of NF-kB inactivation in human T-ALL1 cell line

ORGANISM(S): Homo sapiens

PROVIDER: GSE20667 | GEO | 2011/05/07

SECONDARY ACCESSION(S): PRJNA124923

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2011-05-07 | E-GEOD-20667 | biostudies-arrayexpress
| PRJNA124923 | ENA
2015-05-07 | E-GEOD-65863 | biostudies-arrayexpress
2011-12-12 | E-GEOD-26366 | biostudies-arrayexpress
2015-05-07 | GSE65863 | GEO
2020-07-27 | GSE130614 | GEO
2013-06-01 | GSE47466 | GEO
2006-12-02 | GSE6396 | GEO
2011-12-12 | GSE26366 | GEO
2013-06-01 | E-GEOD-47466 | biostudies-arrayexpress