14 research outputs found
Structural Stability of Human Protein Tyrosine Phosphatase ρ Catalytic Domain: Effect of Point Mutations
Protein tyrosine phosphatase ρ (PTPρ) belongs to the classical receptor type IIB family of protein tyrosine phosphatase, the most frequently mutated tyrosine phosphatase in human cancer. There are evidences to suggest that PTPρ may act as a tumor suppressor gene and dysregulation of Tyr phosphorylation can be observed in diverse diseases, such as diabetes, immune deficiencies and cancer. PTPρ variants in the catalytic domain have been identified in cancer tissues. These natural variants are nonsynonymous single nucleotide polymorphisms, variations of a single nucleotide occurring in the coding region and leading to amino acid substitutions. In this study we investigated the effect of amino acid substitution on the structural stability and on the activity of the membrane-proximal catalytic domain of PTPρ. We expressed and purified as soluble recombinant proteins some of the mutants of the membrane-proximal catalytic domain of PTPρ identified in colorectal cancer and in the single nucleotide polymorphisms database. The mutants show a decreased thermal and thermodynamic stability and decreased activation energy relative to phosphatase activity, when compared to wild- type. All the variants show three-state equilibrium unfolding transitions similar to that of the wild- type, with the accumulation of a folding intermediate populated at ∼4.0 M urea
A Comparison of Medical Management with Misoprostol and Surgical Management for Early Pregnancy Failure
Process evaluation of implementation fidelity in a Danish health-promoting school intervention
Collagen abundance controls melanoma phenotypes through lineage specific microenvironment sensing
Collagen abundance controls melanoma phenotypes through lineage-specific microenvironment sensing
Without 1α-hydroxylation, the gene expression profile of 25(OH)D3 treatment overlaps deeply with that of 1,25(OH)2D3 in prostate cancer cells
Histone Deacetylase Inhibitor Tributyrin and Vitamin A in Cancer
Bioactive food compounds like vitamin A and the butyrate’s prodrug tributyrin
have preventive activities against different types of cancer, and their use in
association could represent a promising strategy for cancer treatment and che-
moprevention. Both compounds can induce cell differentiation and apoptosis of
neoplastic and preneoplastic cells by means of modulation of gene transcription,
yet they act through different but interconnected mechanisms. Vitamin A acts
through nuclear receptors that are tightly regulated by histone modifications such
as acetylation and DNA methylation. Tributyrin modulates transcription of genes
by HDACs inhibition and histone hyperacetylation. This chapter describes how
epigenetics mediates the antineoplastic and chemopreventive activity of vitamin
A, tributyrin, and their derivatives and how their combination can be used to help
overcome current limitations in cancer treatment and prevention. We also show
how the mechanisms of action of vitamin A and tributyrin have aided in the
development of synthetic and bioengineered compounds like synthetic retinoids
and structured lipids, respectively.UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicin