BACKGROUND: Juvenile hormones (JH) and ecdysteroids control postembryonic development in insects. They serve as valuable targets for pest management. Hence, understanding the molecular mechanisms of their action is of crucial importance. CREB-binding protein (CBP) is a universal transcriptional co-regulator. It controls the expression of several genes including those from hormone signaling pathways through co-activation of many transcription factors. However, the role of CBP during postembryonic development in insects is not well understood. Therefore, we have studied the role of CBP in postembryonic development in Tribolium, a model coleopteran insect. RESULTS: CBP is ubiquitously expressed in the red flour beetle, Tribolium castaneum. RNA interference (RNAi) mediated knockdown of CBP resulted in a decrease in JH induction of Kr-h1 gene expression in Tribolium larvae and led to a block in their development. Moreover, the injection of CBP double-stranded RNA (dsRNA) showed lethal phenotypes within 8 days of injection. RNA-seq and subsequent differential gene expression analysis identified CBP target genes in Tribolium. Knockdown of CBP caused a decrease in the expression of 1306 genes coding for transcription factors and other proteins associated with growth and development. Depletion of CBP impaired the expression of several JH response genes (e.g., Kr-h1, Hairy, early trypsin) and ecdysone response genes (EcR, E74, E75, and broad complex). Further, GO enrichment analyses of the downregulated genes showed enrichment in different functions including developmental processes, pigmentation, anatomical structure development, regulation of biological and cellular processes, etc. CONCLUSION: These data suggest diverse but crucial roles for CBP during postembryonic development in the coleopteran model insect, Tribolium. It can serve as a target for RNAi mediated pest management of this stored product pest.

• MeSH
• exprese genu MeSH
• hmyzí proteiny antagonisté a inhibitory   genetika   metabolismus   fyziologie   MeSH
• juvenilní hormony farmakologie   MeSH
• larva genetika   metabolismus   MeSH
• protein vázající CREB antagonisté a inhibitory   genetika   metabolismus   fyziologie   MeSH
• RNA interference MeSH
• Tribolium genetika   růst a vývoj   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

BACKGROUND: Steroid receptor coactivators p300 and CBP are highly expressed in advanced prostate cancer. They potentiate activation of androgen receptor by androgens and anti-androgens. In the present study, we have addressed the question whether these coactivators enhance activity of estrogen receptor-beta (ER-β), which is variably expressed in prostate cancers. METHODS: Expression levels of the coactivators p300 and CBP were manipulated by plasmid or siRNA transfections and activity of ER-β was measured by luciferase assays. Viability was measured by MTT assays and cellular migration was determined by wound-healing and Boyden chamber assays. RESULTS: High expression of ER-β was found in PC3 cells which were used for the experiments. p300 or CBP enhanced activation of ER-β by genistein. Antiestrogens did not acquire agonistic properties in the presence of increased concentrations of either coactivator. Inhibition of p300 or CBP decreased genistein stimulation of ER-β. Genistein reduced migration of PC3 prostate cancer cells and down-regulation of p300 potentiated this effect. CONCLUSIONS: p300 and CBP are implicated in regulation of ER-β activity and cellular migration in prostate cancer. These findings are important for understanding of action of ER-β in carcinoma of the prostate.

• MeSH
• beta receptor estrogenů genetika   fyziologie   MeSH
• genistein farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory prostaty patologie   MeSH
• pohyb buněk účinky léků   MeSH
• protein p300 asociovaný s E1A fyziologie   MeSH
• protein vázající CREB fyziologie   MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH