DCUN1D1 Is an Essential Regulator of Prostate Cancer Proliferation and Tumour Growth That Acts through Neddylation of Cullin 1, 3, 4A and 5 and Deregulation of Wnt/Catenin Pathway

Detalhes bibliográficos
Autor(a) principal: Vava, Akhona
Data de Publicação: 2023
Outros Autores: Paccez, JD, Wang, Yihong, Gu, Xuesong, Bhasin, Manoj K., Myers, Michael, Soares, Nelson C., Libermann, Towia, Zerbini, Luiz
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/160670
Resumo: Funding Information: This research was funded by the International Centre for Genetic Engineering and Biotechnology (ICGEB). A.V. was funded by The South African National Research Foundation (NRF) Scarce Skills Doctoral scholarship and ICGEB fellowship; J.D.P. was funded by ICGEB Arturo Falaschi post-doctoral fellowship, and The South African National Research Foundation (NRF) Support for Rated and Unrated Researchers (Grant number SRUG2205067513); M.M. was funded by the ICGEB; N.C.S. was funded by University of Sharjah Targeted grant number 2301101775; T.A.L. was funded by NIH 1R21 CA187843–01; L.F.Z. was funded by the ICGEB. Publisher Copyright: © 2023 by the authors.
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spelling DCUN1D1 Is an Essential Regulator of Prostate Cancer Proliferation and Tumour Growth That Acts through Neddylation of Cullin 1, 3, 4A and 5 and Deregulation of Wnt/Catenin PathwayDCUN1D1E3 ligaseneddylationprostate cancerWnt/β-catenin pathwayBiochemistry, Genetics and Molecular Biology(all)SDG 3 - Good Health and Well-beingFunding Information: This research was funded by the International Centre for Genetic Engineering and Biotechnology (ICGEB). A.V. was funded by The South African National Research Foundation (NRF) Scarce Skills Doctoral scholarship and ICGEB fellowship; J.D.P. was funded by ICGEB Arturo Falaschi post-doctoral fellowship, and The South African National Research Foundation (NRF) Support for Rated and Unrated Researchers (Grant number SRUG2205067513); M.M. was funded by the ICGEB; N.C.S. was funded by University of Sharjah Targeted grant number 2301101775; T.A.L. was funded by NIH 1R21 CA187843–01; L.F.Z. was funded by the ICGEB. Publisher Copyright: © 2023 by the authors.Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) is an E3 ligase for the neddylation, a post-translational process similar to and occurring in parallel to ubiquitin proteasome pathway. Although established as an oncogene in a variety of squamous cell carcinomas, the precise role of DCUN1D1 in prostate cancer (PCa) has not been previously explored thoroughly. Here, we investigated the role of DCUN1D1 in PCa and demonstrated that DCUN1D1 is upregulated in cell lines as well as human tissue samples. Inhibition of DCUN1D1 significantly reduced PCa cell proliferation and migration and remarkably inhibited xenograft formation in mice. Applying both genomics and proteomics approaches, we provide novel information about the DCUN1D1 mechanism of action. We identified CUL3, CUL4B, RBX1, CAND1 and RPS19 proteins as DCUN1D1 binding partners. Our analysis also revealed the dysregulation of genes associated with cellular growth and proliferation, developmental, cell death and cancer pathways and the WNT/β-catenin pathway as potential mechanisms. Inhibition of DCUN1D1 leads to the inactivation of β-catenin through its phosphorylation and degradation which inhibits the downstream action of β-catenin, reducing its interaction with Lef1 in the Lef1/TCF complex that regulates Wnt target gene expression. Together our data point to an essential role of the DCUN1D1 protein in PCa which can be explored for potential targeted therapy.Centre for Toxicogenomics and Human Health (ToxOmics)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNVava, AkhonaPaccez, JDWang, YihongGu, XuesongBhasin, Manoj K.Myers, MichaelSoares, Nelson C.Libermann, TowiaZerbini, Luiz2023-11-28T22:37:39Z2023-082023-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/160670eng2073-4409PURE: 76715454https://doi.org/10.3390/cells12151973info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:43:25Zoai:run.unl.pt:10362/160670Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:58:09.977018Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv DCUN1D1 Is an Essential Regulator of Prostate Cancer Proliferation and Tumour Growth That Acts through Neddylation of Cullin 1, 3, 4A and 5 and Deregulation of Wnt/Catenin Pathway
title DCUN1D1 Is an Essential Regulator of Prostate Cancer Proliferation and Tumour Growth That Acts through Neddylation of Cullin 1, 3, 4A and 5 and Deregulation of Wnt/Catenin Pathway
spellingShingle DCUN1D1 Is an Essential Regulator of Prostate Cancer Proliferation and Tumour Growth That Acts through Neddylation of Cullin 1, 3, 4A and 5 and Deregulation of Wnt/Catenin Pathway
Vava, Akhona
DCUN1D1
E3 ligase
neddylation
prostate cancer
Wnt/β-catenin pathway
Biochemistry, Genetics and Molecular Biology(all)
SDG 3 - Good Health and Well-being
title_short DCUN1D1 Is an Essential Regulator of Prostate Cancer Proliferation and Tumour Growth That Acts through Neddylation of Cullin 1, 3, 4A and 5 and Deregulation of Wnt/Catenin Pathway
title_full DCUN1D1 Is an Essential Regulator of Prostate Cancer Proliferation and Tumour Growth That Acts through Neddylation of Cullin 1, 3, 4A and 5 and Deregulation of Wnt/Catenin Pathway
title_fullStr DCUN1D1 Is an Essential Regulator of Prostate Cancer Proliferation and Tumour Growth That Acts through Neddylation of Cullin 1, 3, 4A and 5 and Deregulation of Wnt/Catenin Pathway
title_full_unstemmed DCUN1D1 Is an Essential Regulator of Prostate Cancer Proliferation and Tumour Growth That Acts through Neddylation of Cullin 1, 3, 4A and 5 and Deregulation of Wnt/Catenin Pathway
title_sort DCUN1D1 Is an Essential Regulator of Prostate Cancer Proliferation and Tumour Growth That Acts through Neddylation of Cullin 1, 3, 4A and 5 and Deregulation of Wnt/Catenin Pathway
author Vava, Akhona
author_facet Vava, Akhona
Paccez, JD
Wang, Yihong
Gu, Xuesong
Bhasin, Manoj K.
Myers, Michael
Soares, Nelson C.
Libermann, Towia
Zerbini, Luiz
author_role author
author2 Paccez, JD
Wang, Yihong
Gu, Xuesong
Bhasin, Manoj K.
Myers, Michael
Soares, Nelson C.
Libermann, Towia
Zerbini, Luiz
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centre for Toxicogenomics and Human Health (ToxOmics)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Vava, Akhona
Paccez, JD
Wang, Yihong
Gu, Xuesong
Bhasin, Manoj K.
Myers, Michael
Soares, Nelson C.
Libermann, Towia
Zerbini, Luiz
dc.subject.por.fl_str_mv DCUN1D1
E3 ligase
neddylation
prostate cancer
Wnt/β-catenin pathway
Biochemistry, Genetics and Molecular Biology(all)
SDG 3 - Good Health and Well-being
topic DCUN1D1
E3 ligase
neddylation
prostate cancer
Wnt/β-catenin pathway
Biochemistry, Genetics and Molecular Biology(all)
SDG 3 - Good Health and Well-being
description Funding Information: This research was funded by the International Centre for Genetic Engineering and Biotechnology (ICGEB). A.V. was funded by The South African National Research Foundation (NRF) Scarce Skills Doctoral scholarship and ICGEB fellowship; J.D.P. was funded by ICGEB Arturo Falaschi post-doctoral fellowship, and The South African National Research Foundation (NRF) Support for Rated and Unrated Researchers (Grant number SRUG2205067513); M.M. was funded by the ICGEB; N.C.S. was funded by University of Sharjah Targeted grant number 2301101775; T.A.L. was funded by NIH 1R21 CA187843–01; L.F.Z. was funded by the ICGEB. Publisher Copyright: © 2023 by the authors.
publishDate 2023
dc.date.none.fl_str_mv 2023-11-28T22:37:39Z
2023-08
2023-08-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/160670
url http://hdl.handle.net/10362/160670
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2073-4409
PURE: 76715454
https://doi.org/10.3390/cells12151973
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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