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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Format: | Article |
Language: | English |
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Elsevier
2022-01-01
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Series: | Computational and Structural Biotechnology Journal |
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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. |
first_indexed | 2024-04-11T05:19:50Z |
format | Article |
id | doaj.art-b8e0ab877d47413691d8d751d7cf9aa6 |
institution | Directory Open Access Journal |
issn | 2001-0370 |
language | English |
last_indexed | 2024-04-11T05:19:50Z |
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publisher | Elsevier |
record_format | Article |
series | Computational and Structural Biotechnology Journal |
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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