GNL3L inhibits activity of estrogen-related receptor gamma by competing for coactivator binding.
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 (ERRgamma) as a GNL3L-specific binding protein. GNL3L and ERRgamma are coexpressed in the eye, kidney and muscle, and co-reside in the nucleoplasm. The interaction between GNL3L and ERRgamma requires the intermediate domain of GNL3L and the AF2-domain of ERRgamma. 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 ERRgamma. This work reveals a novel mechanism that negatively regulates the transcriptional function of ERRgamma by GNL3L through coactivator competition.
Yasumoto
Hiroaki
H
Center for Cancer and Stem Cell Biology, Alkek Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
Meng
Lingjun
L
Lin
Tao
T
Zhu
Qubo
Q
Tsai
Robert Y L
RY
D000818:Animals; D001667:Binding, Competitive; D002466:Cell Nucleolus / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011960:Receptors, Estrogen / Q000302:isolation & purification / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
C524643:GNL3L protein, mouse; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D011960:Receptors, Estrogen; D014157:Transcription Factors; C425824:estrogen receptor gamma; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1; D019204:GTP-Binding Proteins