Identifying novel SMYD3 interactors on the trail of cancer hallmarks

Computational and Structural Biotechnology Journal

Martina Lepore Signorile¹  Giovanna Forte²  Candida Fasano²  Paola Sanese²  Katia De Marco²  Valentina Grossi²  Cristiano Simone² 

[1] Corresponding authors at: Medical Genetics, National Institute for Gastroenterology, IRCCS ‘S. de Bellis’ Research Hospital, Castellana Grotte (Ba), Italy (C.Fasano, C. Simone).;Medical Genetics, National Institute for Gastroenterology, IRCCS ‘S. de Bellis’ Research Hospital, Castellana Grotte (Ba), Italy;

关键词: Gastrointestinal cancer cell lines;    Hallmarks of cancer;    In silico tripeptide screening;    SMYD3;    SMYD3 interactome;   

DOI  :  

来源: DOAJ

【 摘 要 】

SMYD3 overexpression in several human cancers highlights its crucial role in carcinogenesis. Nonetheless, SMYD3 specific activity in cancer development and progression is currently under debate. Taking advantage of a library of rare tripeptides, which we first tested for their in vitro binding affinity to SMYD3 and then used as in silico probes, we recently identified BRCA2, ATM, and CHK2 as direct SMYD3 interactors. To gain insight into novel SMYD3 cancer-related roles, here we performed a comprehensive in silico analysis to cluster all potential SMYD3-interacting proteins identified by screening the human proteome for the previously tested tripeptides, based on their involvement in cancer hallmarks. Remarkably, we identified mTOR, BLM, MET, AMPK, and p130 as new SMYD3 interactors implicated in cancer processes. Further studies are needed to characterize the functional mechanisms underlying these interactions. Still, these findings could be useful to devise novel therapeutic strategies based on the combined inhibition of SMYD3 and its newly identified molecular partners. Of note, our in silico methodology may be useful to search for unidentified interactors of other proteins of interest.

【 授权许可】

Unknown