RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells

Autores
Ferretti, Valeria Alejandra; Canzoneri, Romina; Palma, Sabina; Lacunza, Ezequiel; Aldaz, Claudio Marcelo; Abba, Martín Carlos
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Rhomboid pseudoproteases are catalytically inactive members of the rhomboid superfamily that modulate the traffic, turnover and activity of their target proteins. Rhomboid domain containing 2 (RHBDD2) is a rhomboid family member overexpressed during mammary gland development and advanced stages of breast cancer. Interactome profiling studies have identified RHBDD2 as a novel binding partner of WW domain‑containing oxidoreductase (WWOX) protein. The present study characterized the RHBDD2‑WWOX interaction in proliferating and differentiated stages of normal mammary and breast cancer cells by co-immunoprecipitation and confocal microscopy. Normal breast and proliferating cancer cells showed significantly increased RHBDD2 mRNA levels compared with their differentiated counterparts. WWOX mRNA was primarily expressed in differentiated cells. WWOX co‑precipitated with RHBDD2, indicating that endogenous RHBDD2 and WWOX were physically associated in normal and breast cancer proliferating cells compared with the differentiated stage. Co‑localization assays corroborated the co‑immunoprecipitation results, demonstrating the RHBDD2‑WWOX protein interaction in normal and proliferating breast cancer cells. RHBDD2 harbors a conserved LPPY motif at the C‑terminus region that directly interacted with the WW domains of WWOX. Since WWOX serves as an inhibitor of the TGFβ/SMAD3 signaling pathway in breast cells, modulation of SMAD3 target genes was analyzed in proliferating and differentiated mammary cells and in RHBDD2 silencing assays. Increased expression levels of SMAD3‑regulated genes were detected in proliferating cells compared with their differentiated counterparts. Follistatin and angiopoietin‑like 4 mRNA was significantly downregulated in RHBDD2 transiently silenced cells compared with scrambled control small interfering RNA. Based on these results, WWOX was suggested to be a novel RHBDD2 target protein involved in the modulation of breast epithelial cell proliferation and differentiation.
Fil: Ferretti, Valeria Alejandra. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Canzoneri, Romina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Palma, Sabina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Lacunza, Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Aldaz, Claudio Marcelo. University of Texas; Estados Unidos
Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Materia
BREAST CANCER
RHOMBOID DOMAIN CONTAINING 2
TGFΒ SIGNALING
WW DOMAIN-CONTAINING OXIDOREDUCTASE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/164675
Acceder
id CONICETDig_c73d72e97f8dc1c6337d5960827d5707
oai_identifier_str oai:ri.conicet.gov.ar:11336/164675
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cellsFerretti, Valeria AlejandraCanzoneri, RominaPalma, SabinaLacunza, EzequielAldaz, Claudio MarceloAbba, Martín CarlosBREAST CANCERRHOMBOID DOMAIN CONTAINING 2TGFΒ SIGNALINGWW DOMAIN-CONTAINING OXIDOREDUCTASEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Rhomboid pseudoproteases are catalytically inactive members of the rhomboid superfamily that modulate the traffic, turnover and activity of their target proteins. Rhomboid domain containing 2 (RHBDD2) is a rhomboid family member overexpressed during mammary gland development and advanced stages of breast cancer. Interactome profiling studies have identified RHBDD2 as a novel binding partner of WW domain‑containing oxidoreductase (WWOX) protein. The present study characterized the RHBDD2‑WWOX interaction in proliferating and differentiated stages of normal mammary and breast cancer cells by co-immunoprecipitation and confocal microscopy. Normal breast and proliferating cancer cells showed significantly increased RHBDD2 mRNA levels compared with their differentiated counterparts. WWOX mRNA was primarily expressed in differentiated cells. WWOX co‑precipitated with RHBDD2, indicating that endogenous RHBDD2 and WWOX were physically associated in normal and breast cancer proliferating cells compared with the differentiated stage. Co‑localization assays corroborated the co‑immunoprecipitation results, demonstrating the RHBDD2‑WWOX protein interaction in normal and proliferating breast cancer cells. RHBDD2 harbors a conserved LPPY motif at the C‑terminus region that directly interacted with the WW domains of WWOX. Since WWOX serves as an inhibitor of the TGFβ/SMAD3 signaling pathway in breast cells, modulation of SMAD3 target genes was analyzed in proliferating and differentiated mammary cells and in RHBDD2 silencing assays. Increased expression levels of SMAD3‑regulated genes were detected in proliferating cells compared with their differentiated counterparts. Follistatin and angiopoietin‑like 4 mRNA was significantly downregulated in RHBDD2 transiently silenced cells compared with scrambled control small interfering RNA. Based on these results, WWOX was suggested to be a novel RHBDD2 target protein involved in the modulation of breast epithelial cell proliferation and differentiation.Fil: Ferretti, Valeria Alejandra. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Canzoneri, Romina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Palma, Sabina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Lacunza, Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Aldaz, Claudio Marcelo. University of Texas; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaSpandidos Publications2021-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/164675Ferretti, Valeria Alejandra; Canzoneri, Romina; Palma, Sabina; Lacunza, Ezequiel; Aldaz, Claudio Marcelo; et al.; RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells; Spandidos Publications; Oncology Reports; 46; 2; 8-2021; 1-81021-335XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3892/or.2021.8108info:eu-repo/semantics/altIdentifier/url/https://www.spandidos-publications.com/10.3892/or.2021.8108info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:29:16Zoai:ri.conicet.gov.ar:11336/164675instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:29:16.872CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells
title RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells
spellingShingle RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells
Ferretti, Valeria Alejandra
BREAST CANCER
RHOMBOID DOMAIN CONTAINING 2
TGFΒ SIGNALING
WW DOMAIN-CONTAINING OXIDOREDUCTASE
title_short RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells
title_full RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells
title_fullStr RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells
title_full_unstemmed RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells
title_sort RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells
dc.creator.none.fl_str_mv Ferretti, Valeria Alejandra
Canzoneri, Romina
Palma, Sabina
Lacunza, Ezequiel
Aldaz, Claudio Marcelo
Abba, Martín Carlos
author Ferretti, Valeria Alejandra
author_facet Ferretti, Valeria Alejandra
Canzoneri, Romina
Palma, Sabina
Lacunza, Ezequiel
Aldaz, Claudio Marcelo
Abba, Martín Carlos
author_role author
author2 Canzoneri, Romina
Palma, Sabina
Lacunza, Ezequiel
Aldaz, Claudio Marcelo
Abba, Martín Carlos
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv BREAST CANCER
RHOMBOID DOMAIN CONTAINING 2
TGFΒ SIGNALING
WW DOMAIN-CONTAINING OXIDOREDUCTASE
topic BREAST CANCER
RHOMBOID DOMAIN CONTAINING 2
TGFΒ SIGNALING
WW DOMAIN-CONTAINING OXIDOREDUCTASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Rhomboid pseudoproteases are catalytically inactive members of the rhomboid superfamily that modulate the traffic, turnover and activity of their target proteins. Rhomboid domain containing 2 (RHBDD2) is a rhomboid family member overexpressed during mammary gland development and advanced stages of breast cancer. Interactome profiling studies have identified RHBDD2 as a novel binding partner of WW domain‑containing oxidoreductase (WWOX) protein. The present study characterized the RHBDD2‑WWOX interaction in proliferating and differentiated stages of normal mammary and breast cancer cells by co-immunoprecipitation and confocal microscopy. Normal breast and proliferating cancer cells showed significantly increased RHBDD2 mRNA levels compared with their differentiated counterparts. WWOX mRNA was primarily expressed in differentiated cells. WWOX co‑precipitated with RHBDD2, indicating that endogenous RHBDD2 and WWOX were physically associated in normal and breast cancer proliferating cells compared with the differentiated stage. Co‑localization assays corroborated the co‑immunoprecipitation results, demonstrating the RHBDD2‑WWOX protein interaction in normal and proliferating breast cancer cells. RHBDD2 harbors a conserved LPPY motif at the C‑terminus region that directly interacted with the WW domains of WWOX. Since WWOX serves as an inhibitor of the TGFβ/SMAD3 signaling pathway in breast cells, modulation of SMAD3 target genes was analyzed in proliferating and differentiated mammary cells and in RHBDD2 silencing assays. Increased expression levels of SMAD3‑regulated genes were detected in proliferating cells compared with their differentiated counterparts. Follistatin and angiopoietin‑like 4 mRNA was significantly downregulated in RHBDD2 transiently silenced cells compared with scrambled control small interfering RNA. Based on these results, WWOX was suggested to be a novel RHBDD2 target protein involved in the modulation of breast epithelial cell proliferation and differentiation.
Fil: Ferretti, Valeria Alejandra. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Canzoneri, Romina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Palma, Sabina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Lacunza, Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Aldaz, Claudio Marcelo. University of Texas; Estados Unidos
Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
description Rhomboid pseudoproteases are catalytically inactive members of the rhomboid superfamily that modulate the traffic, turnover and activity of their target proteins. Rhomboid domain containing 2 (RHBDD2) is a rhomboid family member overexpressed during mammary gland development and advanced stages of breast cancer. Interactome profiling studies have identified RHBDD2 as a novel binding partner of WW domain‑containing oxidoreductase (WWOX) protein. The present study characterized the RHBDD2‑WWOX interaction in proliferating and differentiated stages of normal mammary and breast cancer cells by co-immunoprecipitation and confocal microscopy. Normal breast and proliferating cancer cells showed significantly increased RHBDD2 mRNA levels compared with their differentiated counterparts. WWOX mRNA was primarily expressed in differentiated cells. WWOX co‑precipitated with RHBDD2, indicating that endogenous RHBDD2 and WWOX were physically associated in normal and breast cancer proliferating cells compared with the differentiated stage. Co‑localization assays corroborated the co‑immunoprecipitation results, demonstrating the RHBDD2‑WWOX protein interaction in normal and proliferating breast cancer cells. RHBDD2 harbors a conserved LPPY motif at the C‑terminus region that directly interacted with the WW domains of WWOX. Since WWOX serves as an inhibitor of the TGFβ/SMAD3 signaling pathway in breast cells, modulation of SMAD3 target genes was analyzed in proliferating and differentiated mammary cells and in RHBDD2 silencing assays. Increased expression levels of SMAD3‑regulated genes were detected in proliferating cells compared with their differentiated counterparts. Follistatin and angiopoietin‑like 4 mRNA was significantly downregulated in RHBDD2 transiently silenced cells compared with scrambled control small interfering RNA. Based on these results, WWOX was suggested to be a novel RHBDD2 target protein involved in the modulation of breast epithelial cell proliferation and differentiation.
publishDate 2021
dc.date.none.fl_str_mv 2021-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/164675
Ferretti, Valeria Alejandra; Canzoneri, Romina; Palma, Sabina; Lacunza, Ezequiel; Aldaz, Claudio Marcelo; et al.; RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells; Spandidos Publications; Oncology Reports; 46; 2; 8-2021; 1-8
1021-335X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/164675
identifier_str_mv Ferretti, Valeria Alejandra; Canzoneri, Romina; Palma, Sabina; Lacunza, Ezequiel; Aldaz, Claudio Marcelo; et al.; RHBDD2-WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells; Spandidos Publications; Oncology Reports; 46; 2; 8-2021; 1-8
1021-335X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3892/or.2021.8108
info:eu-repo/semantics/altIdentifier/url/https://www.spandidos-publications.com/10.3892/or.2021.8108
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Spandidos Publications
publisher.none.fl_str_mv Spandidos Publications
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846082762575970304
score 13.22299

Publicaciones similares