Akt phosphorylates Tal1 oncoprotein and inhibits its repressor activity.
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.
Palamarchuk
Alexey
A
Human Cancer Genetics Program, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210, USA.
Efanov
Alexey
A
Maximov
Vadim
V
Aqeilan
Rami I
RI
Croce
Carlo M
CM
Pekarsky
Yuri
Y
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013912:Threonine / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013912:Threonine; D014157:Transcription Factors; C067143:TAL1 protein, human; C494918:AKT1 protein, human