RESUMEN
We report cloning and some features of a novel human gene, MATH2, which encodes a protein of 337 amino acid residues with a basic helix loop helix domain and exhibits 98% similarity to mouse Math2. Results of Northern blot analysis revealed two transcripts of the MATH2 gene of 1.7 kb and 2.4 kb in human brain. We localized MATH2 to chromosome 7 at 7p14-15 by matching with the Human Genome Sequence Database. Human MATH2 and mouse Math2 may have the same functions in the nervous system.
Asunto(s)
Proteínas del Tejido Nervioso , Factores de Transcripción/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Mapeo Cromosómico , Cromosomas Humanos Par 7/genética , Clonación Molecular , ADN Complementario/genética , Secuencias Hélice-Asa-Hélice/genética , Humanos , Ratones , Datos de Secuencia Molecular , Homología de Secuencia de AminoácidoRESUMEN
Understanding the mechanism underlying multidrug resistance and identifying effective targets that can overcome it is of critical importance. In this study, mRNA and miRNA expression profiling of the drug resistant sublines, SGC7901/VCR and SGC7901/ADR, and their parental gastric cancer cell line SGC7901 were performed. A significant number of genes and a limited subset of miRNAs were commonly dysregulated, which were further validated using qRT-PCR. GO and KEGG pathway analyses of the commonly dysregulated genes indicated that the MAPK signalling pathway may be involved in multidrug resistance, which was further validated using immunoblotting and MTT assay. Finally a primary multidrug resistance network in gastric cancer, consisting of the commonly dysregulated genes and miRNAs, was established and functional miRNA-mRNA pairs were identified. The commonly dysregulated genes and miRNAs identified in this study may represent good therapeutic targets and further study of these targets may increase our understanding of the mechanisms underlying multidrug resistance.
Asunto(s)
Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/genética , MicroARNs/genética , ARN Mensajero/genética , Neoplasias Gástricas/genética , Línea Celular Tumoral , Genómica , Humanos , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
The kelch-repeat protein family is a recently found new kind of actin-binding protein. It is characterized by tandemly arranged motifs of about 50 amino acids. Previous study showed that most members of the kelch-repeat family were cytoskeletal proteins implicated in various cellular processes, such as actin cytoskeleton interaction, cytoplasmic sequestration of transcription factors and cell morphology. And some of the family members play important roles in tissue development, such as human ENC-1, NRP/B, etc. Another characteristic of the kelch family is that most members have another conserved BTB domain at the extreme amino terminus. The BTB domain is also found at the N-terminus of 5-10% of zinc-finger transcription factor types and is a conserved protein-protein interaction motif. During the large-scale sequencing analysis of a human fetal brain cDNA library we found a novel kelch-like protein gene 5, KLHL5, KLHL5 has high identity with Drosophila kelch protein and many other family members. Here we report a novel splicing variants of KLHL5, named KLHL5b and the expression pattern of KLHL5b in many tissues.