Disease relevance of Tal1

• The helix-loop-helix transcription factor Tal1 is required for blood cell development and its activation is a frequent event in T-cell acute lymphoblastic leukemia [1].
• Activation of the basic helix-loop-helix (bHLH) gene TAL-1 (or SCL) is the most frequent gain-of-function mutation in pediatric T cell acute lymphoblastic leukemia (T-ALL) [2].
• The DNA binding activity of TAL-1 is not required to induce leukemia/lymphoma in mice [2].
• Similarly, mis-expression of tal-1 in the thymus of transgenic mice results in the development of clonal T cell lymphoblastic leukemia [2].
• We report here that the important proangiogenic stimulus hypoxia stimulates phosphorylation, ubiquitination, and proteasomal breakdown of TAL1 in endothelial cells [3].

Psychiatry related information on Tal1

• TAL1 was as effective as Id in both transcriptional suppression and inhibition of differentiation [4].

High impact information on Tal1

• The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages [5].
• To define roles in other lineages, we studied the hematopoietic potential of homozygous mutant SCL/tal-1 -/- embryonic stem cells upon in vitro differentiation and in vivo in chimeric mice [5].
• These findings suggest that SCL/tal-1 functions very early in hematopoietic development, either in specification of ventral mesoderm to a blood cell fate, or in formation or maintenance of immature progenitors [5].
• The T cell leukemia oncoprotein SCL/tal-1, a basic-helix-loop-helix transcription factor, is required for production of embryonic red blood cells in the mouse yolk sac [5].
• Here we show that in the absence of SCL/tal-1, hematopoiesis, Including the generation of red cells, myeloid cells, megakaryocytes, mast cells, and both T and B lymphoid cells, is undetectable [5].

Biological context of Tal1

• These results suggest that the expression of CD41, a candidate target gene of SCL/Tal1, and c-kit define the divergence of definitive hematopoiesis from endothelial cells during development [6].
• Thus, these data indicate that Akt interacts with Tal1 and regulates Tal1 by phosphorylation at Thr90 in a phosphatidylinositol 3-kinase-dependent manner [1].
• TAL1 oncogene encodes a helix-loop-helix transcription factor, Tal1, which is required for blood cell development, and its activation is a frequent event in T-cell acute lymphoblastic leukemia [7].
• Our results suggest that Tal1 overexpression in B cells results in a phenotype similar to that of B cells of E47/E2A knockout animals [7].
• SCL/TAL1 is a hematopoietic-specific transcription factor of the basic helix-loop-helix (bHLH) family that is essential for erythropoiesis [8].

Anatomical context of Tal1

• We propose a model in which the combinatorial effects of Flk1 and Tal1 act to regulate cell fate choice in early development into hematopoietic, endothelial, and smooth muscle lineages [9].
• Murine hematopoietic stem cells (HSCs) originate from mesoderm in a process that requires the transcription factor SCL/Tal1 [6].
• Tal1 transgenic expression reveals absence of B lymphocytes [7].
• Using our co-culture system with stromal cells, we demonstrate that enforced expression of the transcription factor PU.1 under tetracycline control in Tal1-null embryonic stem (ES) cells rescues the development of osteoclasts and macrophage-like phagocytes [10].
• Here we show multiple functions of Stem cell leukaemia (Scl, also known as Tal1), which encodes a basic helix-loop-helix (bHLH) transcription factor, in the regulation of both astrocyte versus oligodendrocyte cell fate acquisition and V2b versus V2a interneuron cell fate acquisition in the p2 domain of the developing vertebrate spinal cord [11].

Associations of Tal1 with chemical compounds

• Previous work established that the TAL1 proteins are phosphorylated exclusively on serine and identified Ser122 as a substrate for the mitogen-activated protein kinase ERK-1 [12].
• These finger-like cells were positive for mesodermal and/or hemangioblastic markers of kinase insert domain receptor (KDR) and T-cell acute lymphocytic leukemia 1 (TAL1), and produced large amounts of protein tyrosine phosphatase, receptor type, C-positive hematopoietic cells [13].
• In addition, leukemogenesis is accelerated dramatically by transgenic co-expression of tal-1 and the catalytic subunit of casein kinase IIalpha (CKIIalpha), a serine/threonine protein kinase known to modulate the activity of other bHLH transcription factors [14].
• Transcription factor T-cell acute lymphocytic leukemia 1 (Tal-1) is essential for the specification of hematopoietic development [10].
• Stem cell seeding efficiency and the proportion of CFU-S in the S phase after cytosine arabinoside (Ara C) treatments were assessed [15].

Physical interactions of Tal1

• TAL1 encodes a bHLH protein that exhibits sequence-specific DNA binding activity when it forms dimers with another bHLH protein such as E2A [4].

Regulatory relationships of Tal1

• Stem cell homing to the injured tissue is regulated through stromal cell derived factor-1 (SDF-1) and its receptor CXCR4 [16].
• We show that ectopic expression of TAL1 blocks the ability of the bHLH gene myogenin to induce myotube differentiation in C3H10T1/2 cells [4].
• Here we have shown that TAL1 and the ubiquitously expressed murine bHLH transcription factor ALF1 formed heterodimers that, compared with ALF1 homodimers, had a more restricted E-box specificity and bound preferentially to the glucocorticoid-responsive E-box (Egre) motif (AACAGATGGT) [17].
• Our studies suggest that hemangioblast specification within Flk-1 expressing mesoderm is regulated by Scl expression [18].
• Stem cell-mediated muscle regeneration is enhanced by local isoform of insulin-like growth factor 1 [19].

Other interactions of Tal1

• Combinatorial effects of Flk1 and Tal1 on vascular and hematopoietic development in the mouse [9].
• Identification of a TAL1 target gene reveals a positive role for the LIM domain-binding protein Ldb1 in erythroid gene expression and differentiation [20].
• Complete inhibition of their activities through transgenic overexpression of their inhibitors Id1 and Tal1 leads to a dramatic loss of thymocytes [21].
• This disruption of hematopoiesis probably occurs because interaction of Lmo2 protein with factors such as Tal1/Scl is precluded [22].
• These data suggest that the C-terminal domain of TAL1 may directly mask the transactivation domain of E2A-related proteins [4].
• Chromatin immunoprecipitation confirmed that both Runx genes are direct targets of Scl in the fetal liver and that Runx1 is also occupied by Scl in the yolk sac [23].

Analytical, diagnostic and therapeutic context of Tal1

• Here we show in mice that the transcription factor Scl is critical for platelet production after chemotherapy and in thrombopoiesis induced by administration of TPO [24].
• MATERIALS AND METHODS: Protein interactions of LIM-modified LMO2 constructs with TAL1, LDB1, and GATAs were examined in an immunoprecipitation assay [25].
• Here we assess by conditional gene targeting whether SCL/tal-1 is required continuously for the identity and function of HSCs [26].
• To help clarify its role in postnatal vascular processes, we characterized the expression of mouse Tal1 protein by immunocytochemistry in several experimental models of blood vessel formation [27].
• Stem cell-based tissue engineering is a promising technology in the effort to create functional tissues of choice [28].

References