TLE, the human homolog of Groucho, interacts with AML1 and acts as a repressor of AML1-induced transactivation

Yoichi Imai; Mineo Kurokawa; Kozo Tanaka; Alan D. Friedman; Seishi Ogawa; Kinuko Mitani; Yoshio Yazaki; Hisamaru Hirai

doi:10.1006/bbrc.1998.9705

TLE, the human homolog of Groucho, interacts with AML1 and acts as a repressor of AML1-induced transactivation

Yoichi Imai, Mineo Kurokawa, Kozo Tanaka, Alan D. Friedman, Seishi Ogawa, Kinuko Mitani, Yoshio Yazaki, Hisamaru Hirai

School of Medicine

Research output: Contribution to journal › Article › peer-review

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Abstract

The AML1 gene encodes DNA-binding proteins that contain the Runt domain and is found at the breakpoints of some translocations associated with leukemias. It has been reported that AML1 plays pivotal roles in myeloid differentiation, probably through the transcriptional regulation of various hematopoietic genes. Here we demonstrate the physical and the functional interaction between AML1 and TLE1 (transducin-like Enhancer of split) human homolog of Groucho that is known to be a corepressor of Hairy-related proteins. TLE1 binds to AML1 through the Runt domain and the C terminus of AML1 that includes the VWRPY motif. The interaction is mainly mediated by the SP domain of TLE1. Moreover, TLE1 inhibits AML1-induced transactivation of the target promoters through the C terminus of AML1. These results suggest that TLE1 acts as a repressor of AML1 and provide important insights into the mechanism of the negative regulation of the AML1 functions in hematopoiesis and leukemogenesis.

Original language	English (US)
Pages (from-to)	582-589
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	252
Issue number	3
DOIs	https://doi.org/10.1006/bbrc.1998.9705
State	Published - Nov 27 1998

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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title = "TLE, the human homolog of Groucho, interacts with AML1 and acts as a repressor of AML1-induced transactivation",

abstract = "The AML1 gene encodes DNA-binding proteins that contain the Runt domain and is found at the breakpoints of some translocations associated with leukemias. It has been reported that AML1 plays pivotal roles in myeloid differentiation, probably through the transcriptional regulation of various hematopoietic genes. Here we demonstrate the physical and the functional interaction between AML1 and TLE1 (transducin-like Enhancer of split) human homolog of Groucho that is known to be a corepressor of Hairy-related proteins. TLE1 binds to AML1 through the Runt domain and the C terminus of AML1 that includes the VWRPY motif. The interaction is mainly mediated by the SP domain of TLE1. Moreover, TLE1 inhibits AML1-induced transactivation of the target promoters through the C terminus of AML1. These results suggest that TLE1 acts as a repressor of AML1 and provide important insights into the mechanism of the negative regulation of the AML1 functions in hematopoiesis and leukemogenesis.",

author = "Yoichi Imai and Mineo Kurokawa and Kozo Tanaka and Friedman, {Alan D.} and Seishi Ogawa and Kinuko Mitani and Yoshio Yazaki and Hisamaru Hirai",

note = "Funding Information: We thank Dr. S. Stifani and Y. Ito for the gift of the cDNA of TLE1 and mouse PEBP2β, respectively. We also thank Dr. D. Zhang for the gift of pM-CSF-R-luc. This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare and from the Ministry of Education, Science, and Culture of Japan.",

year = "1998",

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doi = "10.1006/bbrc.1998.9705",

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T1 - TLE, the human homolog of Groucho, interacts with AML1 and acts as a repressor of AML1-induced transactivation

AU - Imai, Yoichi

AU - Kurokawa, Mineo

AU - Tanaka, Kozo

AU - Friedman, Alan D.

AU - Ogawa, Seishi

AU - Mitani, Kinuko

AU - Yazaki, Yoshio

AU - Hirai, Hisamaru

N1 - Funding Information: We thank Dr. S. Stifani and Y. Ito for the gift of the cDNA of TLE1 and mouse PEBP2β, respectively. We also thank Dr. D. Zhang for the gift of pM-CSF-R-luc. This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare and from the Ministry of Education, Science, and Culture of Japan.

PY - 1998/11/27

Y1 - 1998/11/27

N2 - The AML1 gene encodes DNA-binding proteins that contain the Runt domain and is found at the breakpoints of some translocations associated with leukemias. It has been reported that AML1 plays pivotal roles in myeloid differentiation, probably through the transcriptional regulation of various hematopoietic genes. Here we demonstrate the physical and the functional interaction between AML1 and TLE1 (transducin-like Enhancer of split) human homolog of Groucho that is known to be a corepressor of Hairy-related proteins. TLE1 binds to AML1 through the Runt domain and the C terminus of AML1 that includes the VWRPY motif. The interaction is mainly mediated by the SP domain of TLE1. Moreover, TLE1 inhibits AML1-induced transactivation of the target promoters through the C terminus of AML1. These results suggest that TLE1 acts as a repressor of AML1 and provide important insights into the mechanism of the negative regulation of the AML1 functions in hematopoiesis and leukemogenesis.

AB - The AML1 gene encodes DNA-binding proteins that contain the Runt domain and is found at the breakpoints of some translocations associated with leukemias. It has been reported that AML1 plays pivotal roles in myeloid differentiation, probably through the transcriptional regulation of various hematopoietic genes. Here we demonstrate the physical and the functional interaction between AML1 and TLE1 (transducin-like Enhancer of split) human homolog of Groucho that is known to be a corepressor of Hairy-related proteins. TLE1 binds to AML1 through the Runt domain and the C terminus of AML1 that includes the VWRPY motif. The interaction is mainly mediated by the SP domain of TLE1. Moreover, TLE1 inhibits AML1-induced transactivation of the target promoters through the C terminus of AML1. These results suggest that TLE1 acts as a repressor of AML1 and provide important insights into the mechanism of the negative regulation of the AML1 functions in hematopoiesis and leukemogenesis.

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TLE, the human homolog of Groucho, interacts with AML1 and acts as a repressor of AML1-induced transactivation

Abstract

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