{"owner": "ArrayExpress Uploader", "pop_total": 0, "id": 3599, "factors": [{"GSM518494 1": {}}, {"GSM518495 1": {}}, {"GSM518496 1": {}}, {"GSM518497 1": {}}, {"GSM542393 1": {}}, {"GSM542394 1": {}}, {"GSM542395 1": {}}, {"GSM542396 1": {}}, {"GSM542397 1": {}}, {"GSM542398 1": {}}, {"GSM542399 1": {}}, {"GSM542400 1": {}}, {"GSM542401 1": {}}, {"GSM542402 1": {}}, {"GSM542403 1": {}}, {"GSM542404 1": {}}, {"GSM542405 1": {}}, {"GSM542406 1": {}}, {"GSM542407 1": {}}, {"GSM542408 1": {}}], "ownerprofile_id": "arrayexpress_sid", "platform": 4, "summary_wrapped": "The NF-\u03baB pathway is a critical regulator of the immune system and has been implicated in cellular transformation and tumorigenesis. NF-...", "pubmed_id": 20832754, "geo_gse_id": "E-GEOD-20667", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 0, "sample_count": 20, "tags": ["cell", "disease", "immune system", "leukemia", "line", "notch"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "the-notchhes1-pathway-sustains-nf-b-activation-thr", "geo_id_plat": "E-GEOD-20667_A-AFFY-44", "name": "The Notch/Hes1 pathway sustains NF-\u03baB activation through CYLD repression in T cell leukemia", "created": "Sep.15, 2014", "summary": "The NF-\u03baB pathway is a critical regulator of the immune system and has been implicated in cellular transformation and tumorigenesis. NF-\u03baB response is regulated by the activation state of the I\u03baB kinase (IKK) complex and triggered by a wide spectrum of stimuli. We previously reported that NF-\u03baB is downstream of Notch1 in T cell acute lymphoblastic leukaemia (T-ALL), however both the mechanisms involving Notch1-induced NF-\u03baB activation and the potential importance of NF-\u03baB in the maintenance of the disease are unknown. Here we visualize Notch-induced NF-\u03baB 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 Twenty samples were analyzed: human T-ALL, CEM, KOPT-K, DND41, HPB-ALL cells lines have been treated at 100uM for 16 hours with control peptide or IKK\u03b3 Nemo binding domain (NBD) inhibitory peptide, that specifically block the canonical NF-\u03baB activity by disrupting the interaction of IKK\u03b3 to IKK\u03b2 and IKK\u03b1", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-20667", "species": "human", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-20667/samples/"}