RESUMO
In this issue of Science Signaling, Somssich and co-workers use fluorescence techniques to show the dynamics that occur during the activation of two different receptor complexes in living plant cells.
Assuntos
Nicotiana/metabolismo , Peptídeos/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de SinaisRESUMO
The transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha) is an important regulator of hepatic lipid metabolism. While PPARalpha is known to activate transcription of numerous genes, no comprehensive picture of PPARalpha binding to endogenous genes has yet been reported. To fill this gap, we performed Chromatin immunoprecipitation (ChIP)-chip in combination with transcriptional profiling on HepG2 human hepatoma cells treated with the PPARalpha agonist GW7647. We found that GW7647 increased PPARalpha binding to 4220 binding regions. GW7647-induced binding regions showed a bias around the transcription start site and most contained a predicted PPAR binding motif. Several genes known to be regulated by PPARalpha, such as ACOX1, SULT2A1, ACADL, CD36, IGFBP1 and G0S2, showed GW7647-induced PPARalpha binding to their promoter. A GW7647-induced PPARalpha-binding region was also assigned to SREBP-targets HMGCS1, HMGCR, FDFT1, SC4MOL, and LPIN1, expression of which was induced by GW7647, suggesting cross-talk between PPARalpha and SREBP signaling. Our data furthermore demonstrate interaction between PPARalpha and STAT transcription factors in PPARalpha-mediated transcriptional repression, and suggest interaction between PPARalpha and TBP, and PPARalpha and C/EBPalpha in PPARalpha-mediated transcriptional activation. Overall, our analysis leads to important new insights into the mechanisms and impact of transcriptional regulation by PPARalpha in human liver and highlight the importance of cross-talk with other transcription factors.
Assuntos
Regulação da Expressão Gênica , PPAR alfa/metabolismo , Regiões Promotoras Genéticas , Sítios de Ligação , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Análise por Conglomerados , Perfilação da Expressão Gênica , Humanos , Neoplasias Hepáticas , Análise de Sequência com Séries de Oligonucleotídeos , Sítio de Iniciação de TranscriçãoAssuntos
Adenosina Trifosfatases/fisiologia , Proteínas de Arabidopsis/fisiologia , Proteínas de Ciclo Celular/fisiologia , Receptores de Superfície Celular/fisiologia , Adenosina Trifosfatases/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Ciclo Celular/metabolismo , Modelos Moleculares , Proteínas Quinases/metabolismo , Proteínas Quinases/fisiologia , Sinais Direcionadores de Proteínas , Transdução de Sinais , Ubiquitina/fisiologia , Proteína com ValosinaRESUMO
Leucine-rich repeat (LRR)-containing transmembrane receptor-like kinases (RLKs) are important components of plant signal transduction. The Arabidopsis thaliana somatic embryogenesis receptor-like kinase 1 (AtSERK1) is an LRR-RLK proposed to participate in a signal transduction cascade involved in embryo development. By yeast two-hybrid screening we identified AtCDC48, a homologue of the mammalian AAA-ATPase p97 and GF14lambda, a member of the Arabidopsis family of 14-3-3 proteins as AtSERK1 interactors. In vitro, the AtSERK1 kinase domain is able to transphosphorylate and bind both AtCDC48 and GF14lambda. In yeast, AtCDC48 interacts with GF14lambda and with the PP2C phosphatase KAPP. In plant protoplasts AtSERK1 interacts with GF14lambda.