Eukaryotic Initiation Factor 5A Plays an Essential Role in Luteinizing Hormone Receptor Regulation

Overview

Journal Mol Endocrinol

Specialties Endocrinology
Molecular Biology

Date 2014 Sep 13

PMID 25216047

Citations 4

Authors

Bindu Menon

Thippeswamy Gulappa

K M J Menon

Affiliations

Soon will be listed here.

Abstract

Down-regulation of LH receptor (LHR) in the ovary by its ligand is mediated by a specific RNA-binding protein, designated LH receptor mRNA-binding protein (LRBP), through translational suppression and mRNA degradation. Using yeast 2-hybrid screens, we previously identified eukaryotic initiation factor 5A (eIF5A) as one of the proteins that interacts with LRBP during LHR mRNA down-regulation. The present study examined the role of eIF5A and its hypusination in the context of LHR mRNA down-regulation. The association of eIF5A with LRBP or LHR mRNA was determined using immunoprecipitation and RNA immunoprecipitation assays. The results showed that the association of eIF5A with the LHR mRNA-LRBP complex increased significantly during down-regulation. Furthermore, gel fractionation and the hypusination activity assay both showed increased hypusination of eIF5A during LHR mRNA down-regulation. Abolishment of hypusination by pretreatment with the chemical inhibitor GC7 prevented the association of eIF5A with LHR mRNA and LRBP. Inhibition of hypusination also reduced the extent of ligand-induced down-regulation of LHR mRNA as well as the expression of functional LHRs assessed by real-time PCR and (125)I-human chorionic gonadotropin (hCG) binding assays, respectively. The loss of human chorionic gonadotropin-mediated downstream signaling during LHR down-regulation was also restored by inhibition of hypusination of eIF5A. Thus, the present study, for the first time, reveals the crucial role of eIF5A and its hypusination in the regulation of LHR expression in the ovary.

Citing Articles

Regulation of gene expression by translation factor eIF5A: Hypusine-modified eIF5A enhances nonsense-mediated mRNA decay in human cells.

Hoque M, Park J, Chang Y, Luchessi A, Cambiaghi T, Shamanna R Translation (Austin). 2017; 5(2):e1366294.

PMID: 29034140 PMC: 5630042. DOI: 10.1080/21690731.2017.1366294.

LHCGR Expression During Follicle Stimulating Hormone-Induced Follicle Growth Is Negatively Regulated by Eukaryotic Initiation Factor 5A.

Gulappa T, Menon B, Menon K Endocrinology. 2017; 158(8):2672-2679.

PMID: 28605466 PMC: 5551546. DOI: 10.1210/en.2017-00113.

The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited.

Rosenfield R, Ehrmann D Endocr Rev. 2016; 37(5):467-520.

PMID: 27459230 PMC: 5045492. DOI: 10.1210/er.2015-1104.

Hypusination of eukaryotic initiation factor 5A via cAMP-PKA-ERK1/2 pathway is required for ligand-induced downregulation of LH receptor mRNA expression in the ovary.

Gulappa T, Menon B, Menon K Mol Cell Endocrinol. 2015; 413:90-5.

PMID: 26116232 PMC: 4523407. DOI: 10.1016/j.mce.2015.06.014.

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