Your browser doesn't support javascript.
loading
Capping Enzyme mRNA-cap/RNGTT Regulates Hedgehog Pathway Activity by Antagonizing Protein Kinase A.
Chen, Ping; Zhou, Zizhang; Yao, Xia; Pang, Shu; Liu, Meijing; Jiang, Weirong; Jiang, Jin; Zhang, Qing.
Afiliación
  • Chen P; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, 210061, China.
  • Zhou Z; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, 210061, China.
  • Yao X; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, 210061, China.
  • Pang S; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, 210061, China.
  • Liu M; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, 210061, China.
  • Jiang W; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, 210061, China.
  • Jiang J; Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390, USA. jin.jiang@utsouthwestern.edu.
  • Zhang Q; Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390, USA. jin.jiang@utsouthwestern.edu.
Sci Rep ; 7(1): 2891, 2017 06 06.
Article en En | MEDLINE | ID: mdl-28588207
Hedgehog (Hh) signaling plays a pivotal role in animal development and its deregulation in humans causes birth defects and several types of cancer. Protein Kinase A (PKA) modulates Hh signaling activity through phosphorylating the transcription factor Cubitus interruptus (Ci) and G protein coupled receptor (GPCR) family protein Smoothened (Smo) in Drosophila, but how PKA activity is regulated remains elusive. Here, we identify a novel regulator of the Hh pathway, the capping-enzyme mRNA-cap, which positively regulates Hh signaling activity through modulating PKA activity. We provide genetic and biochemical evidence that mRNA-cap inhibits PKA kinase activity to promote Hh signaling. Interestingly, regulation of Hh signaling by mRNA-cap depends on its cytoplasmic capping-enzyme activity. In addition, we show that the mammalian homolog of mRNA-cap, RNGTT, can replace mRNA-cap to play the same function in the Drosophila Hh pathway and that knockdown of Rngtt in cultured mammalian cells compromised Shh pathway activity, suggesting that RNGTT is functionally conserved. Our study makes an unexpected link between the mRNA capping machinery and the Hh signaling pathway, unveils a new facet of Hh signaling regulation, and reveals a potential drug target for modulating Hh signaling activity.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Caperuzas de ARN / ARN Mensajero / Transducción de Señal / Proteínas Quinasas Dependientes de AMP Cíclico / Proteínas Hedgehog / Nucleotidiltransferasas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Caperuzas de ARN / ARN Mensajero / Transducción de Señal / Proteínas Quinasas Dependientes de AMP Cíclico / Proteínas Hedgehog / Nucleotidiltransferasas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido