A novel isoform of human LZIP negatively regulates the transactivation of the glucocorticoid receptor

Hyereen Kang, Suk Kim Yoon, Je Sang Ko

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The human leucine zipper protein (LZIP) is a basic leucine zipper transcription factor that is involved in leukocyte migration, tumor suppression, and endoplasmic reticulum stress-associated protein degradation. Although evidence suggests a diversity of roles for LZIP, its function is not fully understood, and the subcellular localization of LZIP is still controversial. We identified a novel isoform of LZIP and characterized its function in ligand-induced transactivation of the glucocorticoid receptor (GR) in COS-7 and HeLa cells. A novel isoform of human LZIP designated as "sLZIP" contains a deleted putative transmembrane domain (amino acids 229-245) of LZIP and consists of 345 amino acids. LZIP and sLZIP were ubiquitously expressed in a variety of cell lines and tissues, with LZIP being much more common. sLZIP was mainly localized in the nucleus, whereas LZIP was located in the cytoplasm. Unlike LZIP, sLZIP was not involved in the chemokine-mediated signal pathway. sLZIP recruited histone deacetylases (HDACs) to the promoter region of the mouse mammary tumor virus luciferase reporter gene and enhanced the activities of HDACs, resulting in suppression of expression of the GR target genes. Our findings suggest that sLZIP functions as a negative regulator in glucocorticoid-induced transcriptional activation of GR by recruitment and activation of HDACs.

Original languageEnglish
Pages (from-to)1746-1757
Number of pages12
JournalMolecular Endocrinology
Volume23
Issue number11
DOIs
Publication statusPublished - 2009 Nov 1

Fingerprint

Leucine Zippers
Glucocorticoid Receptors
Transcriptional Activation
Protein Isoforms
Proteins
Histone Deacetylases
Basic-Leucine Zipper Transcription Factors
Mouse mammary tumor virus
Amino Acids
Endoplasmic Reticulum Stress
COS Cells
Heat-Shock Proteins
Luciferases
Reporter Genes
HeLa Cells
Chemokines
Genetic Promoter Regions
Glucocorticoids
Proteolysis
Signal Transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

A novel isoform of human LZIP negatively regulates the transactivation of the glucocorticoid receptor. / Kang, Hyereen; Yoon, Suk Kim; Ko, Je Sang.

In: Molecular Endocrinology, Vol. 23, No. 11, 01.11.2009, p. 1746-1757.

Research output: Contribution to journalArticle

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