Neuregulin 1-alpha regulates phosphorylation, acetylation, and alternative splicing in lymphoblastoid cells.
Neuregulins (NRGs) are signaling molecules involved in various cellular and developmental processes. Abnormal expression and (or) genomic variations of some of these molecules, such as NRG1, have been associated with disease conditions such as cancer and schizophrenia. To gain a comprehensive molecular insight into possible pathways/networks regulated by NRG1-alpha, we performed a global expression profiling analysis on lymphoblastoid cell lines exposed to NRG1-alpha. Our data show that this signaling molecule mainly regulates coordinated expression of genes involved in three processes: phosphorylation, acetylation, and alternative splicing. These processes have fundamental roles in proper development and function of various tissues including the central nervous system (CNS)--a fact that may explain conditions associated with NRG1 dysregulations such as schizophrenia. The data also suggest NRG1-alpha regulates genes (FBXO41) and miRNAs (miR-33) involved in cholesterol metabolism. Moreover, RPN2, a gene already shown to be dysregulated in breast cancer cells, is also differentially regulated by NRG1-alpha treatment.
a The Centre for Applied Genomics, Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON M5G 1L7, Canada.
Mohammad M
MM
Ghahramani Seno
Fuad G
FG
Gwadry
Pingzhao
P
Hu
Stephen W
SW
Scherer
D000107:Acetylation; D017398:Alternative Splicing; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D005786:Gene Expression Regulation; D063990:Gene Ontology; D006602:Hexosyltransferases; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D020890:Neuregulin-1 / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D020033:Protein Isoforms / Q000494:pharmacology / Q000502:physiology; D012559:Schizophrenia / Q000235:genetics*; D015398:Signal Transduction; D059467:Transcriptome
C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D020890:Neuregulin-1; D020033:Protein Isoforms; D002784:Cholesterol; D006602:Hexosyltransferases; C517590:RPN2 protein, human; D046988:Proteasome Endopeptidase Complex