RESUMO
In a model study to investigate the consequence of reactions of intrinsically disordered regions (IDRs) of proteins in the context of the formation of highly ordered structures, we found that enzymatic reactions control the secondary structures of peptides during assembly. Specifically, phosphorylation of an α-helix-dominant peptide results in mostly disordered conformations, which become ß-strand-dominant after enzymatic dephosphorylation to regenerate the peptide. In the presence of another peptide largely with a ß-strand conformation, direct coassembly of the peptides results in amorphous aggregates consisting of α-helix and ß-strand peptides, but the enzymatically generated peptide coassemblies (from the phosphopeptide) mainly adopt a ß-strand conformation and form ordered structures (e.g., nanofibers). These results indicate that enzymatic dephosphorylation instructs conformationally flexible peptides to adopt thermodynamically favorable conformations in homotypic or heterotypic supramolecular assemblies.
Assuntos
Proteínas Intrinsicamente Desordenadas/química , Peptídeos/química , Biocatálise , Modelos Moleculares , Nanofibras/química , Nanofibras/ultraestrutura , Fosfopeptídeos/química , Fosforilação , Agregados Proteicos , Estrutura Secundária de Proteína , TermodinâmicaRESUMO
FLOT1, a scaffold protein of lipid rafts, is involved in several biological processes, including lipid raft protein-dependent or clathrinindependent endocytosis, and the formation of hippocampal synapses, amongst others. Increasing evidence has shown that FLOT1 can function as both a cancer promoter and cancer suppressor dependent on the type of cancer. FLOT1 can affect the occurrence and development of several types of cancer by affecting epithelialmesenchymal transition, proliferation of cancer cells, and relevant signaling pathways, and is regulated by long intergenic noncoding RNAs or microRNAs. In the nervous system, overexpression or abnormally low expression of FLOT1 may lead to the occurrence of neurological diseases, such as Alzheimer's disease, Parkinson's disease, major depressive disorder and other diseases. Additionally, it is also associated with dilated cardiomyopathy, pathogenic microbial infection, diabetesrelated diseases, and gynecological diseases, amongst other diseases. In the present review, the structure and localization of FLOT1, as well as the physiological processes it is involved in are reviewed, and then the upstream and downstream regulation of FLOT1 in human disease, particularly in different types of cancer and neurological diseases are discussed, with a focus on potentially targeting FLOT1 for the clinical treatment of several diseases.
Assuntos
Transtorno Depressivo Maior , MicroRNAs , Humanos , Linhagem Celular Tumoral , MicroRNAs/genética , Transdução de SinaisRESUMO
Endocrine therapy (ET), also known as hormone therapy, refers to the treatment of tumors by regulating and changing the endocrine environment and hormone levels. Its related mechanism is mainly through reducing hormone levels and blocking the binding of hormones to corresponding receptors, thus blocking the signal transduction pathway to stimulate tumor growth. However, with the application of ET, some patients show resistance to ET, which is attributed to abnormal accumulation of hormone receptors (HRs) and the production of multiple mutants of HRs. The targeted degradation of abnormal accumulation protein mediated by ubiquitination is an important approach that regulates the protein level and function of intracellular proteins in eukaryotes. Here, we provide a brief description of the traditional and novel drugs available for ET in this review. Then, we introduce the link between ubiquitination and ET. In the end, we elaborate the clinical application of ET combined with ubiquitination-related molecules. KEY MESSAGES: ⢠A brief description of the traditional and novel drugs available for endocrine therapy (ET). ⢠The link between ubiquitination and ET. ⢠The clinical application of ET combined with ubiquitination-related molecules.