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dc.contributor.authorKowalski, Thayne Woycinckpt_BR
dc.contributor.authorGomes, Julia do Amaralpt_BR
dc.contributor.authorGarcia, Gabriela Barreto Caldaspt_BR
dc.contributor.authorFraga, Lucas Rosapt_BR
dc.contributor.authorPaixão Côrtes, Vanessa Rodriguespt_BR
dc.contributor.authorRecamonde-Mendoza, Marianapt_BR
dc.contributor.authorSanseverino, Maria Teresa Vieirapt_BR
dc.contributor.authorFaccini, Lavinia Schulerpt_BR
dc.contributor.authorVianna, Fernanda Sales Luizpt_BR
dc.date.accessioned2023-04-07T03:26:05Zpt_BR
dc.date.issued2020pt_BR
dc.identifier.issn2045-2322pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/256799pt_BR
dc.description.abstractThe Cereblon-CRL4 complex has been studied predominantly with regards to thalidomide treatment of multiple myeloma. Nevertheless, the role of Cereblon-CRL4 in Thalidomide Embryopathy (TE) is still not understood. Not all embryos exposed to thalidomide develop TE, hence here we evaluate the role of the CRL4-Cereblon complex in TE variability and susceptibility. We sequenced CRBN, DDB1, CUL4A, IKZF1, and IKZF3 in individuals with TE. To better interpret the variants, we suggested a score and a heatmap comprising their regulatory effect. Differential gene expression after thalidomide exposure and conservation of the CRL4-Cereblon protein complex were accessed from public repositories. Results suggest a summation effect of Cereblon variants on pre-axial longitudinal limb anomalies, and heatmap scores identify the CUL4A variant rs138961957 as potentially having an effect on TE susceptibility. CRL4-Cereblon gene expression after thalidomide exposure and CLR4-Cereblon protein conservation does not explain the difference in Thalidomide sensitivity between species. In conclusion, we suggest that CRL4-Cereblon variants act through several regulatory mechanisms, which may influence CRL4-Cereblon complex assembly and its ability to bind thalidomide. Human genetic variability must be addressed not only to further understand the susceptibility to TE, but as a crucial element in therapeutics, including in the development of pharmacogenomics strategies.en
dc.format.mimetypeapplication/pdfpt_BR
dc.language.isoengpt_BR
dc.relation.ispartofScientific reports. London. Vol. 10 (Jan. 2020), 851, 13 p.pt_BR
dc.rightsOpen Accessen
dc.subjectInformática médicapt_BR
dc.subjectTalidomidapt_BR
dc.titleCRL4-Cereblon complex in Thalidomide Embryopathy : a translational investigationpt_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb001112012pt_BR
dc.type.originEstrangeiropt_BR


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