Functional interactions between erythroid kruppel-like factor (EKLF/KLF1) and protein phosphatase PPM1B/PP2Cβ

Yvette Y. Yien, James J. Bieker

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Erythroid Krüppel-like factor (EKLF; KLF1) is an erythroidspecific transcription factor required for the transcription of genes that regulate erythropoiesis. In this paper, we describe the identification of a novel EKLF interactor, Ppm1b, a serine-threonine protein phosphatase that has been implicated in the attenuation of NFκB signaling and the regulation of Cdk9 phosphorylation status. We show that Ppm1b interacts with EKLF via its PEST1 sequence. However, its genetic regulatory role is complex. Using a promoter-reporter assay in an erythroid cell line, we show that Ppm1b superactivates EKLF at the β-globin and BKLF promoters, dependent on intact Ppm1b phosphatase activity. Conversely, depletion of Ppm1b in CD34+ cells leads to a higher level of endogenous β-globin gene activation after differentiation. We also observe that Ppm1b likely has an indirect role in regulating EKLF turnover via its zinc finger domain. Together, these studies show that Ppm1b plays a multilayered role in regulating the availability and optimal activity of the EKLF protein in erythroid cells.

Original languageEnglish
Pages (from-to)15193-15204
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number19
DOIs
StatePublished - 4 May 2012

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