SENP1 Dominated Desumoylation Of Glil Attenuates Shh Signaling

Sonic Hedgehog(Shh)is an important morphogen regulating the tissue morphogenesis,cell differentiation and embryonic development in mammalian.The core Shh signaling pathway is consist with two membrane receptors,Patched(Ptch)and Smoothened(Smo),and the transcriptional factor(TF)family Gli.As the unique transcriptional factor in Shh signaling pathway,Gli plays the key role in regulating the expression of downstream target genes,and any regulators can affect Shh signaling through regulating Gli,such as SUMO,a post-translational modifier.All of Gli proteins can be modified by SUMO(sumoyaltion),but how does sumoylation regulate its TF function is still unclear now.In our study,we find out two mechanisms by which sumoylation regulates the Shh signaling.Firstly,there is a competitive inhibition between SUMO1 and ubiquitin in the modifying lysine residues on Glil.The increased sumoylation could reduce the ubiquitination level of Glil and enhance its stiblitivity,resulting in a more active transcriptional ability.The other is that sumoylation is required for Glil detained in the nucleus.Without sumoylation,Glil is more easily exported out of the nucleus,and can not turn on the downstream transcription.It is SENP1 who regulates the desumoylation progress of Glil and dominates its sumoyaltion level.In cinclusion,sumoylation enhances the transcriptiongal activity of Glil leading a more active Shh signaling.SENP1,which regulates the desumoylation progress of Glil,plays an inhibitory role of Shh signaling in both intracellular action and physiological function.