RESUMEN
Intrinsically disordered proteins (IDPs) exhibit molecular-level conformational dynamics that are functionally harnessed across a wide range of fascinating biological phenomena. The low sequence complexity of IDPs has led to the design and development of intrinsically-disordered protein polymers (IDPPs), a class of engineered repeat IDPs with stimuli-responsive properties. The perfect repetitive architecture of IDPPs allows for repeat-level encoding of tunable protein functionality. Designer IDPPs can be modeled on endogenous IDPs or engineered de novo as protein polymers with dual biophysical and biological functionality. Their properties can be rationally tailored to access enigmatic IDP biology and to create programmable smart biomaterials. With the goal of inspiring the bioengineering of multifunctional IDP-based materials, here we synthesize recent multidisciplinary progress in programming and exploiting the bio-functionality of IDPPs and IDPP-containing proteins. Collectively, expanding beyond the traditional sequence space of extracellular IDPs, emergent sequence-level control of IDPP functionality is fueling the bioengineering of self-assembling biomaterials, advanced drug delivery systems, tissue scaffolds, and biomolecular condensates -genetically encoded organelle-like structures. Looking forward, we emphasize open challenges and emerging opportunities, arguing that the intracellular behaviors of IDPPs represent a rich space for biomedical discovery and innovation. Combined with the intense focus on IDP biology, the growing landscape of IDPPs and their biomedical applications set the stage for the accelerated engineering of high-value biotechnologies and biomaterials.
Asunto(s)
Sistemas de Liberación de Medicamentos , Proteínas Intrínsecamente Desordenadas , Polímeros , Proteínas Intrínsecamente Desordenadas/química , Humanos , Polímeros/química , Materiales Biocompatibles/química , AnimalesRESUMEN
BACKGROUND/AIM: Triple negative cancer (TNBC) is a subtype of breast cancer that is highly aggressive, with poor prognosis and responds differently to treatments. This study investigated the role of vorinostat and indole-3-carbinol (I3C) on regulating critical receptors that are not normally expressed in TNBC. MATERIALS AND METHODS: Using real-time PCR, immunostaining, and western blots, the re-expression of estrogen receptor α (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) receptors was examined in four different TNBC cell types. RESULTS: ERα was re-expressed in three subtypes using vorinostat and I3C. Re-expression of the PR by vorinostat was also detected. Neither vorinostat nor I3C resulted in re-expression of the HER2 receptor. A significant decrease in growth and sensitivity to tamoxifen was also noted. CONCLUSION: The results of this study show that vorinostat and I3C modulate the re-expression of critical receptors in certain subtypes of TNBC through several pathways and these effects can be influenced by the molecular profiles of TNBCs.