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Published on: July 22, 2020
Identifying novel SMYD3 interactors on the trail of cancer hallmarks
Candida Fasano1, Martina Lepore Signorile1, Katia De Marco1
1Medical Genetics, National Institute for Gastroenterology, IRCCS 'S. de Bellis' Research Hospital, Castellana Grotte (Ba), Italy.
Abstract:
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.
Insights
This study identifies new proteins interacting with SMYD3, a protein involved in cancer. These findings may lead to novel therapeutic strategies targeting cancer development by inhibiting SMYD3 and its partners.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- SMYD3 overexpression is observed in various human cancers, suggesting its role in carcinogenesis.
- The precise function of SMYD3 in cancer development and progression remains under investigation.
- Previous research identified BRCA2, ATM, and CHK2 as direct SMYD3 interactors using tripeptide probes.
Purpose of the Study:
- To identify novel SMYD3-interacting proteins implicated in cancer hallmarks.
- To gain insights into the potential cancer-related roles of SMYD3.
- To explore new therapeutic strategies targeting SMYD3 and its molecular partners.
Main Methods:
- Utilized a library of rare tripeptides to test in vitro binding affinity to SMYD3.
- Employed in silico analysis to screen the human proteome for potential SMYD3 interactors based on tripeptide screening.
- Clustered identified proteins based on their involvement in cancer hallmarks.
Main Results:
- Identified mTOR, BLM, MET, AMPK, and p130 as novel SMYD3 interactors.
- These newly identified interactors are implicated in various cancer processes.
- The in silico methodology proved effective in identifying potential protein interactors.
Conclusions:
- The study expands the known interactome of SMYD3, revealing new potential roles in cancer.
- The identified SMYD3 interactors offer potential targets for novel cancer therapies.
- The in silico approach can be valuable for discovering interactors of other proteins of interest.
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