Mitogen-activated protein kinase mediates erythropoietin-induced phosphorylation of the TAL1/SCL transcription factor in murine proerythroblasts

TANG, Tong; PRASAD, K.S. Srinivasa; KOURY, Mark J.; BRANDT, Stephen J.

doi:10.1042/0264-6021:3430615

Cited by 12 publications

(12 citation statements)

References 46 publications

(66 reference statements)

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“…), pcDNA3L-NLI was provided by Gordon Gill (University of California, San Diego), and pXM-GATA-1 was provided by Leonard Zon (Boston Childrens Hospital, Boston, Mass.). pcDNA3.1-Tal1 was described recently (52), and the analogous pcDNA3.1-E47 was constructed by subcloning an XbaI fragment containing E47 coding sequence from pCMV-E47 into the XbaI site of vector pcDNA3.1. Plasmid pcDNA3.1-GATA-1 was made by similarly transferring an XhoI fragment containing the GATA-1 coding sequence from pXM-GATA-1 into the XhoI site of pcDNA3.1.…”

Section: Methodsmentioning

confidence: 99%

Identification of a TAL1 Target Gene Reveals a Positive Role for the LIM Domain-Binding Protein Ldb1 in Erythroid Gene Expression and Differentiation

Xu¹,

Huang²,

Chang

et al. 2003

Molecular and Cellular Biology

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The TAL1 (or SCL) gene, originally identified from its involvement by a recurrent chromosomal translocation, encodes a basic helix-loop-helix transcription factor essential for erythropoiesis. Although presumed to regulate transcription, its target genes are largely unknown. We show here that a nuclear complex containing TAL1, its DNA-binding partner E47, zinc finger transcription factor GATA-1, LIM domain protein LMO2, and LIM domain-binding protein Ldb1 transactivates the protein 4.2 (P4.2) gene through two E box GATA elements in its proximal promoter. Binding of this complex to DNA was dependent on the integrity of both E box and GATA sites and was demonstrated to occur on the P4.2 promoter in cells. Maximal transcription in transiently transfected cells required both E box GATA elements and expression of all five components of the complex. This complex was shown, in addition, to be capable of linking in solution double-stranded oligonucleotides corresponding to the two P4.2 E box GATA elements. This DNA-linking activity required Ldb1 and increased with dimethyl sulfoxide-induced differentiation of murine erythroleukemia (MEL) cells. In contrast, enforced expression in MEL cells of dimerization-defective mutant Ldb1, as well as wild-type Ldb1, significantly decreased E box GATA DNA-binding activities, P4.2 promoter activity, and accumulation of P4.2 and ␤-globin mRNAs. These studies define a physiologic target for a TAL1-and GATA-1-containing ternary complex and reveal a positive role for Ldb1 in erythroid gene expression and differentiation.Red blood cell production is controlled by the concerted actions of signal transducers and nuclear regulators. Genetargeting studies have demonstrated a requirement for several nuclear proteins in erythropoiesis, including the TAL1 (or SCL) and GATA-1 transcription factors and the LIM domain protein LMO2. These proteins, singly and in combination, bind to specific promoter and enhancer elements to regulate the expression of genes that execute the differentiation program.

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Section: Methodsmentioning

confidence: 99%

Identification of a TAL1 Target Gene Reveals a Positive Role for the LIM Domain-Binding Protein Ldb1 in Erythroid Gene Expression and Differentiation

Xu¹,

Huang²,

Chang

et al. 2003

Molecular and Cellular Biology

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127

158

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“…Metabolic Labeling of Cells and Radioimmunoprecipitation Analysis-MS1 cells were metabolically labeled as described by Tang et al (36). Briefly, cells were incubated in phosphate-free minimum essential medium with 5% dialyzed FBS at 37°C for 1 h and radiolabeled with 0.9 mCi/ml [ 32 P]orthophosphate (ICN) for 1.5 h in the presence of 10 M MG132.…”

Section: Methodsmentioning

confidence: 99%

“…Construction of pcDNA1-Tal1 and pcDNA1-Tal1 S122A plasmids has been described previously (36). To express Myc epitope-tagged Tal1 and Tal1 S122A proteins, the appropriate cDNA was subcloned into vector pcDNA3.1(ϩ) (Invitrogen), and a nucleotide sequence encoding a human c-Myc epitope was inserted by site-directed mutagenesis immediately before the stop codon (GeneEditor In Vitro Site-Directed Mutagenesis System, Promega, Madison, WI).…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, a specific serine in the putative transactivation domain of the protein, Ser 122 , is preferentially phosphorylated by ERK1 in vitro (53) and is the target in cells of epidermal growth factor (EGF)-and erythropoietin-stimulated MAPK phosphorylation (36,53). To determine which residues were phosphorylated in response to hypoxia, two-dimensional tryptic phosphopeptide analysis was carried out on radiolabeled Tal1 immunoprecipitated from hypoxic MS1 cells that had been pretreated with PD98059.…”

Section: Hypoxia Stimulates the Mapk-catalyzed Phosphorylation Of Talmentioning

confidence: 99%

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Phosphorylation by Mitogen-activated Protein Kinase Mediates the Hypoxia-induced Turnover of the TAL1/SCL Transcription Factor in Endothelial Cells

Tang¹,

Arbiser²,

Brandt³

2002

Journal of Biological Chemistry

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The basic helix-loop-helix transcription factor TAL1 (or SCL), originally identified from its involvement by a chromosomal rearrangement in T-cell acute lymphoblastic leukemia, is required for hematopoietic development. TAL1 also has a critical role in embryonic vascular remodeling and is expressed in endothelial cells postnatally, although little is known about its function or regulation in this cell type. We report here that the important proangiogenic stimulus hypoxia stimulates phosphorylation, ubiquitination, and proteasomal breakdown of TAL1 in endothelial cells. Tryptic phosphopeptide mapping and chemical inhibitor studies showed that hypoxia induced the mitogen-activated protein kinase-mediated phosphorylation of a single serine residue, Ser 122 , in the protein, and site-directed mutagenesis demonstrated that Ser 122 phosphorylation was necessary for hypoxic acceleration of TAL1 turnover in an immortalized murine endothelial cell line. Finally, whereas TAL1 expression was detected in endothelial cells from both large and small vessels, hypoxiainduced TAL1 turnover was observed only in microvascular endothelial cells. Besides their implications for TAL1 function in angiogenic processes, these results demonstrate that a protein kinase(s) important for mitogenic signaling is also utilized in hypoxic endothelial cells to target a transcription factor for destruction.The TAL1 (or SCL) gene encodes a basic helix-loop-helix transcription factor originally identified from its involvement by a chromosomal translocation in T-cell acute lymphoblastic leukemia (1, 2). TAL1 coding sequences have also been found fused to the promoter of an adjacent gene, SIL (for SCL interrupting locus), as the result of interstitial deletions (3, 4), whereas in other patients with T-cell acute lymphoblastic leukemia, the gene is expressed in the apparent absence of chromosomal rearrangement (5). Three related genes have also been found to be activated in T-cell acute lymphoblastic leukemia (6 -8), although significantly less frequently than TAL1. In aggregate, overexpression of this subclass of basic helix-loophelix genes is the most common gain of function mutation in this form of leukemia (reviewed in Ref. 9).TAL1 binds DNA with any of the more widely expressed basic helix-loop-helix proteins known as E proteins, including the E12, E47, and E2-5 splice isoforms of the E2A gene, the related E2-2 protein, and the HEB/HTF4 gene products (10, 11). These TAL1-E protein heterodimers recognize a nucleotide motif, CANNTG, termed the E-box to activate or repress transcription (12-15). A variety of adaptor proteins or coregulators, including the LIM domain oncoproteins LMO1 and LMO2 (16,17), histone acetyltransferases p300/CBP (14) and P/CAF (18), and nuclear corepressors mSin3A and mSin3B (15), also interact with TAL1 and modulate its transcriptional properties. With rare exceptions (19), however, TAL1's target genes remain unidentified.TAL1 is a critical regulator of hematopoietic differentiation. Tal1 gene inactivation by homologous reco...

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“…Two phosphorylation sites have been reported to date. Phosphorylation of Ser122 by the mitogen-activated protein kinase extracellular signal-regulated kinase-1 was found to increase the activity of a transcriptional activation domain (5,6). Another serine residue, Ser172, located near the DNA binding domain, can be phosphorylated by cyclic AMP-dependent protein kinase (7).…”

Section: Introductionmentioning

confidence: 99%

Akt Phosphorylates Tal1 Oncoprotein and Inhibits Its Repressor Activity

et al. 2005

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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. The Akt (protein kinase B) kinase is a key player in transduction of antiapoptotic and proliferative signals in T cells. Because Tal1 has a putative Akt phosphorylation site at Thr90, we investigated whether Akt regulates Tal1. Our results show that Akt specifically phosphorylates Thr90 of the Tal1 protein within its transactivation domain in vitro and in vivo. Coimmunoprecipitation experiments showed the presence of Tal1 in Akt immune complexes, suggesting that Tal1 and Akt physically interact. We further showed that phosphorylation of Tal1 by Akt causes redistribution of Tal1 within the nucleus. Using luciferase assay, we showed that phosphorylation of Tal1 by Akt decreased repressor activity of Tal1 on EpB42 (P4.2) promoter. Thus, these data indicate that Akt interacts with Tal1 and regulates Tal1 by phosphorylation at Thr90 in a phosphatidylinositol 3-kinase-dependent manner. (Cancer Res 2005; 65(11): 4515-9)

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Mitogen-activated protein kinase mediates erythropoietin-induced phosphorylation of the TAL1/SCL transcription factor in murine proerythroblasts

Cited by 12 publications

References 46 publications

Identification of a TAL1 Target Gene Reveals a Positive Role for the LIM Domain-Binding Protein Ldb1 in Erythroid Gene Expression and Differentiation

Identification of a TAL1 Target Gene Reveals a Positive Role for the LIM Domain-Binding Protein Ldb1 in Erythroid Gene Expression and Differentiation

Phosphorylation by Mitogen-activated Protein Kinase Mediates the Hypoxia-induced Turnover of the TAL1/SCL Transcription Factor in Endothelial Cells

Akt Phosphorylates Tal1 Oncoprotein and Inhibits Its Repressor Activity

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