Core Transcriptional Regulatory Circuit Controlled by the TAL1 Complex in Human T Cell Acute Lymphoblastic Leukemia
| Autor: | Lee N. Lawton, Richard A. Young, Yebin Ahn, Holger Kohlhammer, Louis M. Staudt, Alejandro Gutierrez, Jessica Tatarek, Wenxue Ma, Zi Peng Fan, Michelle A. Kelliher, A. Thomas Look, Takaomi Sanda, Catriona Jamieson, M. Inmaculada Barrasa |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Cell Survival T-Lymphocytes T-Cell Acute Lymphocytic Leukemia Protein 1 Biology Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Article Proto-Oncogene Proteins c-myb 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Proto-Oncogene Proteins hemic and lymphatic diseases Basic Helix-Loop-Helix Transcription Factors Homeostasis Humans Gene Regulatory Networks MYB Transcription factor 030304 developmental biology Regulation of gene expression 0303 health sciences Gene Expression Regulation Leukemic Genome Human GATA3 Cell Biology Neoplasm Proteins RUNX1 chemistry Oncology 030220 oncology & carcinogenesis Cancer research Genes Neoplasm Protein Binding TAL1 |
| Zdroj: | Cancer Cell. 22(2):209-221 |
| ISSN: | 1535-6108 |
| DOI: | 10.1016/j.ccr.2012.06.007 |
| Popis: | SummaryThe oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of human T cell acute lymphoblastic leukemia (T-ALL), emphasizing its importance in the molecular pathogenesis of T-ALL. Here we identify the core transcriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3, and RUNX1. We show that TAL1 forms a positive interconnected autoregulatory loop with GATA3 and RUNX1 and that the TAL1 complex directly activates the MYB oncogene, forming a positive feed-forward regulatory loop that reinforces and stabilizes the TAL1-regulated oncogenic program. One of the critical downstream targets in this circuitry is the TRIB2 gene, which is oppositely regulated by TAL1 and E2A/HEB and is essential for the survival of T-ALL cells. |
| Databáze: | OpenAIRE |
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