Erythropoietin Prevents Hypoxia-Induced GATA-4 Ubiquitination via Phosphorylation of Serine 105 of GATA-4

DOI Web Site Web Site PubMed 参考文献12件
  • Jun Ji Hae
    Severance Biomedical Science Institute, Yonsei University College of Medicine
  • Shin Eun Jung
    Anesthesia and Pain Research Institute, Yonsei University Health System
  • Kim Ji Ho
    Anesthesia and Pain Research Institute, Yonsei University Health System Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine
  • Kim Si Oh
    Department of Anesthesiology and Pain Medicine, College of Medicine, Kyungpook National University Hospital
  • Shim Jae-Kwang
    Anesthesia and Pain Research Institute, Yonsei University Health System Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine
  • Kwak Young-Lan
    Severance Biomedical Science Institute, Yonsei University College of Medicine Anesthesia and Pain Research Institute, Yonsei University Health System Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine

書誌事項

タイトル別名
  • Erythropoietin Prevents Hypoxia-Induced GATA-4 Ubiquitination <i>via</i> Phosphorylation of Serine 105 of GATA-4

この論文をさがす

抄録

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.

収録刊行物

参考文献 (12)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ