A novel role of CPEB3 in regulating EGFR gene transcription via association with Stat5b in neurons.
CPEB3 is a sequence-specific RNA-binding protein and represses translation of its target mRNAs in neurons. Here, we have identified a novel function of CPEB3 as to interact with Stat5b and inhibit its transcription activity in the nucleus without disrupting dimerization, DNA binding and nuclear localization of Stat5b. Moreover, CPEB3 is a nucleocytoplasm-shuttling protein with predominant residence in the cytoplasm; whereas activation of NMDA receptors accumulates CPEB3 in the nucleus. Using the knockdown approach, we have found the receptor tyrosine kinase, EGFR, is a target gene transcriptionally activated by Stat5b and downregulated by CPEB3 in neurons. The increased EGFR expression in CPEB3 knockdown neurons, when stimulated with EGF, alters the kinetics of downstream signaling. Taken together, CPEB3 has a novel function in the nucleus as to suppress Stat5b-dependent EGFR gene transcription. Consequently, EGFR signaling is negatively regulated by CPEB3 in neurons.
Peng
Shu-Chun
SC
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 104, Taiwan.
Lai
Yen-Ting
YT
Huang
Hsi-Yuan
HY
Huang
Hsien-Da
HD
Huang
Yi-Shuian
YS
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D007858:Learning; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
C513866:CPEB3 protein, human; D016601:RNA-Binding Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D050799:STAT5 Transcription Factor; D066246:ErbB Receptors