Identifying novel SMYD3 interactors on the trail of cancer hallmarks

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 affin...

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Main Authors: Candida Fasano, Martina Lepore Signorile, Katia De Marco, Giovanna Forte, Paola Sanese, Valentina Grossi, Cristiano Simone
Format: Article
Language:English
Published: Elsevier 2022-01-01
Series:Computational and Structural Biotechnology Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S200103702200112X
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author Candida Fasano
Martina Lepore Signorile
Katia De Marco
Giovanna Forte
Paola Sanese
Valentina Grossi
Cristiano Simone
author_facet Candida Fasano
Martina Lepore Signorile
Katia De Marco
Giovanna Forte
Paola Sanese
Valentina Grossi
Cristiano Simone
author_sort Candida Fasano
collection DOAJ
description 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.
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spelling doaj.art-b8e0ab877d47413691d8d751d7cf9aa62022-12-24T04:51:56ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012018601875Identifying novel SMYD3 interactors on the trail of cancer hallmarksCandida Fasano0Martina Lepore Signorile1Katia De Marco2Giovanna Forte3Paola Sanese4Valentina Grossi5Cristiano Simone6Medical Genetics, National Institute for Gastroenterology, IRCCS ‘S. de Bellis’ Research Hospital, Castellana Grotte (Ba), Italy; 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), ItalyMedical Genetics, National Institute for Gastroenterology, IRCCS ‘S. de Bellis’ Research Hospital, Castellana Grotte (Ba), ItalyMedical Genetics, National Institute for Gastroenterology, IRCCS ‘S. de Bellis’ Research Hospital, Castellana Grotte (Ba), ItalyMedical Genetics, National Institute for Gastroenterology, IRCCS ‘S. de Bellis’ Research Hospital, Castellana Grotte (Ba), ItalyMedical Genetics, National Institute for Gastroenterology, IRCCS ‘S. de Bellis’ Research Hospital, Castellana Grotte (Ba), ItalyMedical Genetics, National Institute for Gastroenterology, IRCCS ‘S. de Bellis’ Research Hospital, Castellana Grotte (Ba), Italy; Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari Aldo Moro, Bari, Italy; Corresponding authors at: Medical Genetics, National Institute for Gastroenterology, IRCCS ‘S. de Bellis’ Research Hospital, Castellana Grotte (Ba), Italy (C.Fasano, C. Simone).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.http://www.sciencedirect.com/science/article/pii/S200103702200112XGastrointestinal cancer cell linesHallmarks of cancerIn silico tripeptide screeningSMYD3SMYD3 interactome
spellingShingle Candida Fasano
Martina Lepore Signorile
Katia De Marco
Giovanna Forte
Paola Sanese
Valentina Grossi
Cristiano Simone
Identifying novel SMYD3 interactors on the trail of cancer hallmarks
Computational and Structural Biotechnology Journal
Gastrointestinal cancer cell lines
Hallmarks of cancer
In silico tripeptide screening
SMYD3
SMYD3 interactome
title Identifying novel SMYD3 interactors on the trail of cancer hallmarks
title_full Identifying novel SMYD3 interactors on the trail of cancer hallmarks
title_fullStr Identifying novel SMYD3 interactors on the trail of cancer hallmarks
title_full_unstemmed Identifying novel SMYD3 interactors on the trail of cancer hallmarks
title_short Identifying novel SMYD3 interactors on the trail of cancer hallmarks
title_sort identifying novel smyd3 interactors on the trail of cancer hallmarks
topic Gastrointestinal cancer cell lines
Hallmarks of cancer
In silico tripeptide screening
SMYD3
SMYD3 interactome
url http://www.sciencedirect.com/science/article/pii/S200103702200112X
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