Functional dissection of the alpha and beta subunits of transcription factor PEBP2 and the redox susceptibility of its DNA binding activity.

The Journal of Biological Chemistry
H KagoshimaK Shigesada

Abstract

The mouse transcription factor PEBP2 is a heterodimer of two subunits: a DNA binding subunit alpha and its partner subunit beta. The alpha subunit shares a region of high homology, termed the Runt domain, with the products of the Drosophila melanogaster segmentation gene runt and the human acute myeloid leukemia-related gene AML1. To study the molecular basis for the DNA binding and heterodimerization functions of this factor, we constructed series of deletions of the alpha and beta subunits and examined their activities by electrophoretic mobility shift and affinity column assays. The minimal functional region of the alpha subunit for DNA binding and dimerization was shown to coincide with the Runt domain. On the other hand, the region of the beta subunit required for heterodimerization was localized to the N-terminal 135 amino acids. Furthermore, it was found that the DNA binding activity of the Runt domain is regulated by a reduction/oxidization (redox) mechanism and that its reductively activated state, which is extremely labile, is stabilized by the beta subunit. These findings add a new layer to the mechanism and significance of the regulatory interplay between the two subunits of PEBP2.

References

Apr 9, 1992·Nature·A DagaF Calabi
May 11, 1992·Nucleic Acids Research·S GuehmannK Moelling
Dec 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·H MiyoshiM Ohki
May 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·M B Toledano, W J Leonard
Sep 7, 1995·Biochemical Pharmacology·K Schulze-OsthoffP A Baeuerle
Jan 1, 1994·Annual Review of Immunology·P A Baeuerle, T Henkel
Oct 1, 1993·Trends in Genetics : TIG·H KagoshimaP Gergen
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·E OgawaY Ito
Feb 11, 1993·Nucleic Acids Research·C Wasylyk, B Wasylyk
Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·Q WangN A Speck

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Citations

Aug 4, 2001·Biochemical and Biophysical Research Communications·S SudhakarN Elango
Jan 30, 2002·Gene·John T SwarthoutNicola C Partridge
Apr 17, 1999·Cellular Signalling·H Kamata, H Hirata
May 7, 2003·Blood Cells, Molecules & Diseases·Taketoshi YoshidaKatsuya Shigesada
Nov 16, 2002·Nature Genetics·Mondira KunduP Paul Liu
Jan 5, 2000·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Y Ito
Apr 2, 1999·European Journal of Biochemistry·M Wolf-WatzT Härd
Jan 9, 2007·Journal of Biomolecular Structure & Dynamics·Oded SuadZippora Shakked
Sep 10, 2009·Antioxidants & Redox Signaling·Margarete LukoszJudith Haendeler
May 29, 2003·Nucleic Acids Research·Claire A P Bristow, Paul Shore
Apr 5, 2014·PloS One·Giselle Sek Suan NahByrappa Venkatesh
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·J Y ChoiG S Stein
Aug 28, 1998·Leukemia & Lymphoma·N AsouK Takatsuki
Jul 3, 2007·Gene·Cherry Ee Lin NgYoshiaki Ito
Mar 29, 2000·FEBS Letters·G C Pérez-AlvaradoP E Wright
Jan 30, 2003·Oncogene·Fernando P G SilvaMicheline Giphart-Gassler

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