title: Differential effects of hyperphosphorylation on splicing factor SRp55.
abstract: Members of the serine/arginine-rich (SR) protein family play an important role in both constitutive and regulated splicing of precursor mRNAs. Phosphorylation of the arginine/serine dipeptide-rich domain (RS domain) can modulate the activity and the subcellular localization of SR proteins. However, whether the SR protein family members are individually regulated and how this is achieved remain unclear. In this report we show that 5,6-dichloro-1 beta-D-ribofuranosyl-benzimidazole (DRB), an inhibitor of RNA polymerase II-dependent transcription, specifically induced hyperphosphorylation of SRp55 but not that of any other SR proteins tested. Hyperphosphorylation of SRp55 occurs at the RS domain and appears to require the RNA-binding activity. Upon DRB treatment, hyperphosphorylated SRp55 relocates to enlarged nuclear speckles. Intriguingly, SRp55 is specifically targeted for degradation by the proteasome upon overexpression of the SR protein kinase Clk/Sty. Although a destabilization signal is mapped within the C-terminal 43-amino acid segment of SRp55, its adjacent lysine/serine-rich RS domain is nevertheless critical for the Clk/Sty-mediated degradation. We report for the first time that SRp55 can be hyperphosphorylated under different circumstances whereby its fate is differentially influenced.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Lai
authors.forename: Ru-Inn
authors.initials: RI
authors.lastname: Lin
authors.forename: Woan-Yuh
authors.initials: WY
authors.lastname: Tarn
mesh_terms: D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D009097:Multienzyme Complexes / Q000378:metabolism; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D009097:Multienzyme Complexes; D016601:RNA-Binding Proteins; D004004:Dichlororibofuranosylbenzimidazole; C066780:Clk dual-specificity kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex