Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia.
Cancer Cell, 2012/8/14;22(2):209-21.
Sanda T[1], Lawton LN, Barrasa MI, Fan ZP, Kohlhammer H, Gutierrez A, Ma W, Tatarek J, Ahn Y, Kelliher MA, Jamieson CH, Staudt LM, Young RA, Look AT
Affiliations
PMID: 22897851DOI: 10.1016/j.ccr.2012.06.007
Impact factor: 38.585
Abstract
The 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.
MeSH terms
Basic Helix-Loop-Helix Transcription Factors; Cell Line, Tumor; Cell Survival; Gene Expression Regulation, Leukemic; Gene Regulatory Networks; Genes, Neoplasm; Genome, Human; Homeostasis; Humans; Neoplasm Proteins; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Protein Binding; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-myb; T-Cell Acute Lymphocytic Leukemia Protein 1; T-Lymphocytes
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download