Splicing potentiation by growth factor signals via estrogen receptor phosphorylation.
Mitogen-activated protein kinase-mediated growth factor signals are known to augment the ligand-induced transactivation function of nuclear estrogen receptor alpha (ERalpha) through phosphorylation of Ser-118 within the ERalpha N-terminal transactivation (activation function-1) domain. We identified the spliceosome component splicing factor (SF)3a p120 as a coactivator specific for human ERalpha (hERalpha) activation function-1 that physically associated with ERalpha dependent on the phosphorylation state of Ser-118. SF3a p120 potentiated hERalpha-mediated RNA splicing, and notably, the potentiation of RNA splicing by SF3a p120 depended on hER Ser-118 phosphorylation. Thus, our findings suggest a mechanism by which growth factor signaling can regulate gene expression through the modulation of RNA splicing efficiency via phosphorylation of sequence-specific activators, after association between such activators and the spliceosome.
Masuhiro
Yoshikazu
Y
Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
Mezaki
Yoshihiro
Y
Sakari
Matomo
M
Takeyama
Ken-ichi
K
Yoshida
Tasuku
T
Inoue
Kunio
K
Yanagisawa
Junn
J
Hanazawa
Shigemasa
S
O'malley
Bert W
BW
Kato
Shigeaki
S
D000818:Animals; D002460:Cell Line; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D012326:RNA Splicing / Q000187:drug effects*; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D017381:Spliceosomes / Q000378:metabolism
D047628:Estrogen Receptor alpha; D006133:Growth Substances; D017413:Ribonucleoprotein, U2 Small Nuclear; C088049:splicing factor 3a; D010768:Phosphoserine; D020928:Mitogen-Activated Protein Kinases