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First published online 10 July 2007
doi: 10.1242/jcs.009878

Journal of Cell Science 120, 2532-2543 (2007)
Published by The Company of Biologists 2007
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Research Article

GNL3L inhibits activity of estrogen-related receptor {gamma} by competing for coactivator binding

Hiroaki Yasumoto, Lingjun Meng*, Tao Lin*, Qubo Zhu and Robert Y. L. Tsai{ddagger}

Center for Cancer and Stem Cell Biology, Alkek Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA

{ddagger} Author for correspondence (e-mail: rtsai{at}ibt.tamhsc.edu)

Accepted 22 May 2006

Guanine nucleotide binding protein-like 3 (GNL3L) is the closest homologue of a stem cell-enriched factor nucleostemin in vertebrates. They share the same yeast orthologue, Grn1p, but only GNL3L can rescue the growth-deficient phenotype in Grn1-null yeasts. To determine the unique function of GNL3L, we identified estrogen-related receptor {gamma} (ERR{gamma}) as a GNL3L-specific binding protein. GNL3L and ERR{gamma} are coexpressed in the eye, kidney and muscle, and co-reside in the nucleoplasm. The interaction between GNL3L and ERR{gamma} requires the intermediate domain of GNL3L and the AF2-domain of ERR{gamma}. Gain-of- and loss-of-function experiments show that GNL3L can inhibit the transcriptional activities of ERR genes in a cell-based reporter system, which does not require the nucleolar localization of GNL3L. We further demonstrate that GNL3L is able to reduce the steroid receptor coactivator (SRC) binding and the SRC-mediated transcriptional coactivation of ERR{gamma}. This work reveals a novel mechanism that negatively regulates the transcriptional function of ERR{gamma} by GNL3L through coactivator competition.

Key words: ERR, Estrogen receptor, GNL3L, Nucleolus, Nucleostemin, SRC




This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
L. Meng, Q. Zhu, and R. Y. L. Tsai
Nucleolar Trafficking of Nucleostemin Family Proteins: Common versus Protein-Specific Mechanisms
Mol. Cell. Biol., December 15, 2007; 27(24): 8670 - 8682.
[Abstract] [Full Text] [PDF]


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