A novel isoform of human LZIP negatively regulates the transactivation of the glucocorticoid receptor.
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.
School of Life Sciences and Biotechnology, Korea University, 5-1 Anam-dong, Seongbuk-gu, Seoul 136-701, Korea.
Hyereen
H
Kang
Yoon Suk
YS
Kim
Jesang
J
Ko
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D008969:Molecular Sequence Data; D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015533:Transcriptional Activation
C107941:CREB3 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid