LRF is an essential downstream target of GATA1 in erythroid development and regulates BIM-dependent apoptosis Journal Article

   

Authors:	Maeda, T.; Ito, K.; Merghoub, T.; Poliseno, L.; Hobbs, R. M.; Wang, G.; Dong, L. W.; Maeda, M.; Dore, L. C.; Zelent, A.; Luzzatto, L.; Teruya-Feldstein, J.; Weiss, M. J.; Pandolfi, P. P.
Article Title:	LRF is an essential downstream target of GATA1 in erythroid development and regulates BIM-dependent apoptosis
Abstract:	GATA-1-dependent transcription is essential for erythroid differentiation and maturation. Suppression of programmed cell death is also thought to be critical for this process; however, the link between these two features of erythropoiesis has remained elusive. Here, we show that the POZ-Krüppel family transcription factor, LRF (also known as Zbtb7a/Pokemon), is a direct target of GATA1 and plays an essential antiapoptotic role during terminal erythroid differentiation. We find that loss of Lrf leads to lethal anemia in embryos, due to increased apoptosis of late-stage erythroblasts. This programmed cell death is Arf and p53 independent and is instead mediated by upregulation of the proapoptotic factor Bim. We identify Lrf as a direct repressor of Bim transcription. In strong support of this mechanism, genetic Bim loss delays the lethality of Lrf-deficient embryos and rescues their anemia phenotype. Thus, our data define a key transcriptional cascade for effective erythropoiesis, whereby GATA-1 suppresses BIM-mediated apoptosis via LRF. © 2009 Elsevier Inc. All rights reserved.
Keywords:	controlled study; unclassified drug; nonhuman; protein function; protein analysis; animal cell; mouse; phenotype; animal tissue; apoptosis; cell maturation; erythroblast; erythropoiesis; protein depletion; protein targeting; bim protein; cell differentiation; protein p53; erythroid cell; devbio; upregulation; arf protein; erythroid kruppel like factor; transcription factor gata 1; transcription factor lrf; downstream processing
Journal Title:	Developmental Cell
Volume:	17
Issue:	4
ISSN:	1534-5807
Publisher:	Cell Press
Date Published:	2009-10-20
Start Page:	527
End Page:	540
Language:	English
DOI:	10.1016/j.devcel.2009.09.005
PROVIDER:	scopus
PMCID:	PMC3134301
PUBMED:	19853566
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-70350061670&partnerID=40&md5=76999a26eea163096d1d72d6f9a513f4
Notes:	--- - "Cited By (since 1996): 2" - "Export Date: 30 November 2010" - "CODEN: DCEEB" - "Source: Scopus"

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