Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cells ; 8(11)2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683936

RESUMO

Rad6B, a principal component of the translesion synthesis pathway, and activator of canonical Wnt signaling, plays an essential role in cutaneous melanoma development and progression. As Rad6 is encoded by two genes, namely, UBE2A (RAD6A) and UBE2B (RAD6B), in humans, we compared their expressions in melanomas and normal melanocytes. While both genes are weakly expressed in normal melanocytes, Rad6B is more robustly expressed in melanoma lines and patient-derived metastatic melanomas than RAD6A. The characterization of RAD6B transcripts revealed coexpression of various splice variants representing truncated or modified functional versions of wild-type RAD6B in melanomas, but not in normal melanocytes. Notably, two RAD6B isoforms with intact catalytic domains, RAD6BΔexon4 and RAD6Bintron5ins, were identified. We confirmed that RAD6BΔexon4 and RAD6Bintron5ins variants are expressed as 14 and 15 kDa proteins, respectively, with functional in vivo ubiquitin conjugating activity. Whole exome sequence analysis of 30 patient-derived melanomas showed RAD6B variants coexpressed with wild-type RAD6B in all samples analyzed, and RAD6Bintron5ins variants were found in half the cases. These variants constitute the majority of the RAD6B transcriptome in contrast to RAD6A, which was predominantly wild-type. The expression of functional RAD6B variants only in melanomas reveals RAD6B's molecular heterogeneity and its association with melanoma pathogenesis.


Assuntos
Melanoma/genética , Neoplasias Cutâneas/genética , Enzimas de Conjugação de Ubiquitina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Processamento Alternativo , Linhagem Celular , Reparo do DNA , Replicação do DNA , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/metabolismo , Pessoa de Meia-Idade , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/metabolismo , Transcrição Gênica , Transcriptoma , Enzimas de Conjugação de Ubiquitina/metabolismo , Sequenciamento do Exoma/métodos , Via de Sinalização Wnt , beta Catenina/metabolismo , Melanoma Maligno Cutâneo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...