RRC ID 48858
著者 Chen P, Zhou Z, Yao X, Pang S, Liu M, Jiang W, Jiang J, Zhang Q.
タイトル Capping Enzyme mRNA-cap/RNGTT Regulates Hedgehog Pathway Activity by Antagonizing Protein Kinase A.
ジャーナル Sci Rep
Abstract 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.
巻・号 7(1)
ページ 2891
公開日 2017-6-6
DOI 10.1038/s41598-017-03165-2
PII 10.1038/s41598-017-03165-2
PMID 28588207
PMC PMC5460166
MeSH Animals Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors* Drosophila Proteins / genetics Drosophila Proteins / metabolism Gene Knockdown Techniques Hedgehog Proteins / metabolism* Humans Mice Models, Biological Nucleotidyltransferases / metabolism* Phenotype RNA Caps* RNA, Messenger / genetics* RNA, Messenger / metabolism* Signal Transduction* Wings, Animal
IF 3.998
引用数 3
WOS 分野 CELL BIOLOGY
リソース情報
ショウジョウバエ 7035R-3 3412R-1