Methyltransferase-like 17 physically and functionally interacts with estrogen receptors.
Estrogen exerts its physiological and pathological functions through two estrogen receptors (ERs), ERα and ERβ, which act as transcription factors. Coregulators, including coactivators and corepressors, have been shown to be crucial for regulation of ER transcriptional activity. Although many coregulators have been identified to regulate activities of ERs, novel coregulators are still needed to be investigated. Here, we show that human methyltransferase-like 17 (METTL17), whose function is unknown, physically interacts with ERα and ERβ, and functionally acts as a coactivator for ERs. METTL17 interacts with ER in vitro and in yeast and mammalian cells. Activation function-1 (AF1) and AF2 domains of ERs are responsible for the interaction between METTL17 and ERs. Knockdown of METTL17 reduces transcriptional activities of ERα and ERβ in breast cancer cells, whereas METTL17 overexpression increases ERα and ERβ transcriptional activities. Inhibition of METTL17 expression decreases mRNA and protein levels of ER target genes, including PR, cathepsin D, and pS2. Moreover, METTL17 knockdown reduces breast cancer cell growth. These results indicate that METTL17 is a novel coactivator of ERs and may play a role in breast tumorigenesis.
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Peiyun
P
Du
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Bin
B
Yuan
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Jia
J
Cao
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Jing
J
Zhao
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Lihua
L
Ding
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Lihan
L
Chen
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Sunyang
S
Ying
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Lina
L
Jiang
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Jiajia
J
Lin
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Xiaojie
X
Xu
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Long
L
Cheng
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Qinong
Q
Ye
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004958:Estradiol / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000737:chemistry / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008780:Methyltransferases / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D014158:Transcription, Genetic
C506487:ESR1 protein, human; C000600034:ESR2 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004958:Estradiol; C000611566:METTL17 protein, human; D008780:Methyltransferases
estrogen receptor; methyltransferase-like 17; transcriptional activity