ECNUer has new findings on cellular processes


Qiu Wenwei(Left) and Song Baoliang has some new findings on cellular processes.

On Feb.15 2017, Molecular Cell published an article titled: “Smoothened’s (SMO) Cholesterol Modification Process is Required for the Activation of Hedgehog (Hh)”. The article was written together by Professor Song Baoliang of Wuhan University and Associate Professor Qiu Wenwei of East China Normal University.  

In the article Song and Qiu discuss some new findings in their research on cellular processes. They found that they were able to identify another protein that is also covalently modified by cholesterol--Hedgehog (Hh). It is the first protein identified in the field since 1996 that coveys such a reaction. The results of this discovery also revealed that cholesterol plays a vital role in the cardiovascular and cerebrovascular developments of certain diseases.  

Hh is credited to be the only cholesterol-modified morphogen that serves important functions in cellular development and tumorigenesis. One of the crucial unanswered questions’ is how Hh-signaling regulates the activity of the Smoothened (SMO) molecule.  

SMO is covalently modified by the Cholesterol Probe.

In their research Song and Qiu also performed an unbiased biochemical screen experiment; of which, identified that SMO was modified by cholesterol through the reaction of an ester bond on the residue of Asp95 (D95). Although this particular modification was evident in Patched-1; they point out that this event was even more so facilitated by the Hh molecule.  

The SMO (D95N) mutation; however, could not be modified by cholesterol because it was refractory to the localization of Hh-stimulated ciliary. As a result it failed to activate the cellular downstream-signaling process that is necessary for the transformation. 

According to another study of the homozygous SMO D99N/D99N (this is the equivalent amount to residue in mouse), knockin mice were diagnosed with embryonic-lethal deficiencies that embodied severe cardiac defects. The results of the study suggest that Hh-signaling works with SMO to facilitate its cholesterol modification, provides a therapeutic opportunity to treat Hh pathway-related cancers, and targets SMO’s reaction to cholesterol by means of the transformation.

Molecular Cell is a peer-reviewed scientific journal that focuses on research innovations in the core cellular processes of organisms. 

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East China Normal University