Erythropoietin prevents hypoxia-induced GATA-4 ubiquitination via phosphorylation of serine 105 of GATA-4

Ji Hae Jun, Eun Jung Shin, Ji Ho Kim, Si Oh Kim, Jae Kwang Shim, Younglan Kwak

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Erythropoietin (EPO), an essential hormone for erythropoiesis, can provide protection against myocardial ischemia/reperfusion (I/R) injury and hypoxic apoptosis. GATA-4 is a zinc finger transcription factor, and its activation and post-translational modification are essential components in the transcriptional response to hypoxia. GATA-4 has also been reported to play a role in the cellular mechanisms of EPO-induced myocardial protection against I/R injury. In this study, we aimed to investigate the influence of EPO on GATA-4 protein stability and post-translational modification under hypoxic conditions without reperfusion. EPO induced cell viability under long-term hypoxia. EPO significantly increased phosphorylation of GATA-4 via the extracellular signal-regulated kinase (ERK) signaling pathway and reduced hypoxia-induced GATA-4 ubiquitination, which enhanced GATA-4 stability under hypoxia. ERK activation by over-expression of constitutively active mitogen-activated protein kinase 1 (MEK1) strongly increased GATA-4 phosphorylation and its protein levels and decreased GATA-4 ubiquitination under hypoxia. Despite ERK activation, GATA-4 ubiquitination was not affected under hypoxia in a GATA-4-S105A mutant. Under hypoxic condition without reperfusion, EPO-induced ERK activation was associated with post-translational modification of GATA-4, mediated by enhancement of phosphorylation of GATA-4 at Ser-105. Subsequent attenuation of GATA-4 ubiquitination led to increases in GATA-4 protein stability, which resulted in increased cell viability under hypoxia.

Original languageEnglish
Pages (from-to)1126-1133
Number of pages8
JournalBiological and Pharmaceutical Bulletin
Volume36
Issue number7
DOIs
Publication statusPublished - 2013 Jul 1

Fingerprint

Ubiquitination
Erythropoietin
Serine
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Post Translational Protein Processing
Protein Stability
Reperfusion Injury
Reperfusion
Cell Survival
Myocardial Reperfusion Injury
Erythropoiesis
Mitogen-Activated Protein Kinase 1
Zinc Fingers
Hypoxia
Myocardial Ischemia
Transcription Factors
Hormones
Apoptosis
Proteins

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Jun, Ji Hae ; Shin, Eun Jung ; Kim, Ji Ho ; Kim, Si Oh ; Shim, Jae Kwang ; Kwak, Younglan. / Erythropoietin prevents hypoxia-induced GATA-4 ubiquitination via phosphorylation of serine 105 of GATA-4. In: Biological and Pharmaceutical Bulletin. 2013 ; Vol. 36, No. 7. pp. 1126-1133.
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Erythropoietin prevents hypoxia-induced GATA-4 ubiquitination via phosphorylation of serine 105 of GATA-4. / Jun, Ji Hae; Shin, Eun Jung; Kim, Ji Ho; Kim, Si Oh; Shim, Jae Kwang; Kwak, Younglan.

In: Biological and Pharmaceutical Bulletin, Vol. 36, No. 7, 01.07.2013, p. 1126-1133.

Research output: Contribution to journalArticle

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