[HTML][HTML] Use of altered specificity mutants to probe a specific protein–protein interaction in differentiation: the GATA-1: FOG complex

JD Crispino, MB Lodish, JP MacKay, SH Orkin - Molecular cell, 1999 - cell.com
JD Crispino, MB Lodish, JP MacKay, SH Orkin
Molecular cell, 1999cell.com
GATA-1 and FOG (Friend of GATA-1) are each essential for erythroid and megakaryocyte
development. FOG, a zinc finger protein, interacts with the amino (N) finger of GATA-1 and
cooperates with GATA-1 to promote differentiation. To determine whether this interaction is
critical for GATA-1 action, we selected GATA-1 mutants in yeast that fail to interact with FOG
but retain normal DNA binding, as well a compensatory FOG mutant that restores interaction.
These novel GATA-1 mutants do not promote erythroid differentiation of GATA-1− erythroid …
Abstract
GATA-1 and FOG (Friend of GATA-1) are each essential for erythroid and megakaryocyte development. FOG, a zinc finger protein, interacts with the amino (N) finger of GATA-1 and cooperates with GATA-1 to promote differentiation. To determine whether this interaction is critical for GATA-1 action, we selected GATA-1 mutants in yeast that fail to interact with FOG but retain normal DNA binding, as well a compensatory FOG mutant that restores interaction. These novel GATA-1 mutants do not promote erythroid differentiation of GATA-1 erythroid cells. Differentiation is rescued by the second-site FOG mutant. Thus, interaction of FOG with GATA-1 is essential for the function of GATA-1 in erythroid differentiation. These findings provide a paradigm for dissecting protein–protein associations involved in mammalian development.
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