Open Close
Reference
Citation
Chen, P., Zhou, Z., Yao, X., Pang, S., Liu, M., Jiang, W., Jiang, J., Zhang, Q. (2017). Capping Enzyme mRNA-cap/RNGTT Regulates Hedgehog Pathway Activity by Antagonizing Protein Kinase A.  Sci. Rep. 7(1): 2891.
FlyBase ID
FBrf0235777
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC5460166 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Sci. Rep.
    Title
    Scientific reports
    ISBN/ISSN
    2045-2322
    Data From Reference
    Alleles (34)
    Gene Groups (1)
    Genes (14)
    Physical Interactions (6)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (4)
    Transgenic Constructs (31)