Evi-1 transforming and repressor activities are mediated by CtBP co-repressor proteins

The Journal of Biological Chemistry
S PalmerC Bartholomew

Abstract

Ectopic production of the EVI1 transcriptional repressor zinc finger protein is seen in 4--6% of human acute myeloid leukemias. Overexpression also transforms Rat1 fibroblasts by an unknown mechanism, which is likely to be related to its role in leukemia and which depends upon its repressor activity. We show here that mutant murine Evi-1 proteins, lacking either the N-terminal zinc finger DNA binding domain or both DNA binding zinc finger clusters, function as dominant negative mutants by reverting the transformed phenotype of Evi-1 transformed Rat1 fibroblasts. The dominant negative activity of the non-DNA binding mutants suggests sequestration of transformation-specific cofactors and that recruitment of these cellular factors might mediate Evi-1 transforming activity. C-terminal binding protein (CtBP) co-repressor family proteins bind PLDLS-like motifs. We show that the murine Evi-1 repressor domain has two such sites, PFDLT (site a, amino acids 553--559) and PLDLS (site b, amino acids 584--590), which independently can bind CtBP family co-repressor proteins, with site b binding with higher affinity than site a. Functional analysis of specific CtBP binding mutants show site b is absolutely required to mediate both transformat...Continue Reading

References

May 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·K MorishitaJ N Ihle
Mar 1, 1994·Molecular and Cellular Biology·H MatsushimeJ Y Kato
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·B L KreiderJ N Ihle
Feb 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·S FearsG Nucifora
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·J WangJ M Liu
Nov 20, 1998·Molecular and Cellular Biology·B LutterbachS W Hiebert
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·A A Postigo, D C Dean
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·A R MeloniJ R Nevins
Nov 24, 1999·Molecular and Cellular Biology·T FurusawaY Higashi
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·G M CuencoR Ren

❮ Previous
Next ❯

Citations

Mar 21, 2006·Apoptosis : an International Journal on Programmed Cell Death·L M Bergman, J P Blaydes
Sep 16, 2003·Blood Cells, Molecules & Diseases·Silvia BuonamiciGiuseppina Nucifora
Dec 27, 2011·Nature Neuroscience·Keita EndoAdrian W Moore
Jan 28, 2012·Nature Neuroscience·Dietmar Schmucker, Bassem A Hassan
Jan 30, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jean-Yves Métais, Cynthia E Dunbar
Nov 22, 2005·Oncogene·A G UrenM van Lohuizen
Jun 8, 2002·Molecular and Cellular Biology·Sophie DeltourDominique Leprince
Aug 18, 2005·International Journal of Hematology·Tetsuya YamagataKinuko Mitani
Jun 14, 2013·International Journal of Cell Biology·Jung S Byun, Kevin Gardner
Mar 31, 2004·The Journal of Cell Biology·Alexandra ChittkaMichael Sendtner
Oct 27, 2015·International Journal of Oncology·Xiaofen YuanGuosheng Jiang
Jan 6, 2016·British Journal of Haematology·Adil A Hinai, Peter J M Valk
May 11, 2011·Biochimica Et Biophysica Acta·Anjan Kumar PradhanSoumen Chakraborty
Aug 18, 2010·Biochimica Et Biophysica Acta·Sanchari GhoshUllas Kolthur-Seetharam
Jul 20, 2007·The FEBS Journal·Roger McGilvrayChris Bartholomew
Jul 26, 2008·Journal of Cellular Biochemistry·Francesca Cattaneo, Giuseppina Nucifora
Oct 27, 2011·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Cathrine K FogAnders H Lund
Oct 4, 2006·Gene·Hadi AlzuherriChris Bartholomew
Nov 30, 2005·Gene·Giuseppina NuciforaVitalyi Senyuk
Jun 28, 2005·Cytokine & Growth Factor Reviews·Leo A van GrunsvenKristin Verschueren
Jun 8, 2014·The International Journal of Biochemistry & Cell Biology·Anjan Kumar PradhanSoumen Chakraborty
Jul 12, 2005·The Journal of Biological Chemistry·Bogdan YatsulaArchibald S Perkins
Sep 21, 2006·The Journal of Biological Chemistry·Su-Yan WangQinghong Zhang

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.