摘要:
This invention provides a method for modulating the expression of a first gene in a cell wherein the first gene is one containing more than 36 CAG trinucleotide repeats and encoding a protein that form polyglutamine-mediated protein aggregation. Suppression of the first gene is achieved by reducing the expression of SPT4 gene or SUPT4H gene. It can also be achieved by inhibiting the formation of a Spt4/Spt5 complex or a Supt4h/Supt5h complex. Also provided is a method for identifying an agent useful for modulating the expression and aggregation of CAG-expanded gene product, or treating a polyglutamine disease such as Huntington's disease.
摘要:
This invention provides a method for modulating the expression of a first gene in a cell wherein the first gene is one containing more than 36 CAG trinucleotide repeats and encoding a protein that form polyglutamine-mediated protein aggregation. Suppression of the first gene is achieved by reducing the expression of SPT4 gene or SUPT4H gene. It can also be achieved by inhibiting the formation of a Spt4/Spt5 complex or a Supt4h/Supt5h complex. Also provided is a method for identifying an agent useful for modulating the expression and aggregation of CAG-expanded gene product, or treating a polyglutamine disease such as Huntington's disease.
摘要:
Aspects of the invention include methods of selectively reducing the deleterious activity of mutant extended trinucleotide repeat containing genes in a cell, as well as compositions used in such methods. The deleterious activity (e.g., toxicity and/or dis-functionality of products encoded thereby) of a mutant extended trinucleotide repeat containing gene may be selectively reduced in a variety of different ways, e.g., by selectively decreasing SPT4 mediated transcriptional activity, by enhancing functionality of proteins encoded thereby, etc. Aspects of the invention further include assays for identifying agents that find use in methods of the invention, e.g. as summarized above. Methods and compositions of the invention find use in a variety of different applications, including the prevention or treatment of disease conditions associated with the presence of genes containing mutant extended trinucleotide repeats, such as Huntington's Disease (HD).
摘要:
Aspects of the invention include methods of selectively reducing the deleterious activity of mutant extended trinucleotide repeat containing genes in a cell, as well as compositions used in such methods. The deleterious activity (e.g., toxicity and/or dis-functionality of products encoded thereby) of a mutant extended trinucleotide repeat containing gene may be selectively reduced in a variety of different ways, e.g., by selectively decreasing SPT4 mediated transcriptional activity, by enhancing functionality of proteins encoded thereby, etc. Aspects of the invention further include assays for identifying agents that find use in methods of the invention, e.g. as summarized above. Methods and compositions of the invention find use in a variety of different applications, including the prevention or treatment of disease conditions associated with the presence of genes containing mutant extended trinucleotide repeats, such as Huntington's Disease (HD).
摘要:
TSG101 is a tumor susceptibility gene whose homozygous functional knock out in fibroblasts leads to transformation and the ability of these cells to form metastatic tumors in nude mice. The cellular transformation that results from inactivation of TSG101 is reversible by restoration of TSG101 function. Decreased expression of TSG101 is associated with the occurrence of certain human cancers, including breast carcinomas. The TSG101 nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like. The DNA is further used as a diagnostic for a genetic predisposition to cancer, and to identify specific cancers having mutations in this gene.
摘要:
A method and a DNA linker are described for synthesizing relatively long double-stranded deoxyribonucleic acid sequences of defined composition. Short complementary single strand segments of oligonucleotides comprising part of the full sequence desired are synthesized using known procedures. Overlapping single strand segments are annealed forming double-stranded fragments which are inserted in cloning vectors and cloned in an appropriate host, both purifying the DNA fragments and amplifying the amount thereof. An adjacent fragment is then similarly synthesized in quantity and such fragments are inserted adjacent to the first synthetic introduced fragments in the cloning vectors, followed by cloning in an appropriate host. The procedure continues until the entire desired sequence has been formed, at which time it may be excised or cloned directly in the vectors upon which it was made. The described DNA linker contains a restriction enzyme recognition sequence for a restriction enzyme which cuts offset from the recognition sequence and exactly at the end of the linker, enabling synthesized DNA to be inserted at the end of the linker without disturbing the recognition sequence.
摘要:
Methods and compositions for enhancing taxane sensitivity are provided. Aspects of the subject methods include administering to a subject a txr1 pathway modulatory agent in conjunction with a taxane. Also provided are txr1 polypeptides and nucleic acids encoding the same. The subject methods and compositions find use in a variety of different applications.
摘要:
TSG101 is a tumor susceptibility gene whose homozygous functional knock out in fibroblasts leads to transformation and the ability of these cells to form metastatic tumors in nude mice. The cellular transformation that results from inactivation of TSG101 is reversible by restoration of TSG101 function. Decreased expression of TSG101 is associated with the occurrence of certain human cancers, including breast carcinomas. The TSG101 nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like. The DNA is further used as a diagnostic for a genetic predisposition to cancer, and to identify specific cancers having mutations in this gene.
摘要:
The present invention provides methods and compositions for regulating ubiquitination in a cell. In particular, the present invention provides purified polypeptides comprising an ubiquitination-regulating domain. The invention also provides methods of using such polypeptides for screening for agents, for producing antibodies, and for treatment of diseases, e.g., proliferative diseases, neurodegenerative diseases, autoimmune diseases, metabolic disease and developmental abnormalities. The invention further provides antibodies that bind an ubiquitination-regulating domain and agents and antibodies that regulate ubiquitination in cells, e.g., by modulating the interaction between a TSG101 protein and an MDM2 protein.
摘要:
TSG101 is a tumor susceptibility gene whose homozygous functional knock out in fibroblasts leads to transformation and the ability of these cells to form metastatic tumors in nude mice. The cellular transformation that results from inactivation of TSG101 is reversible by restoration of TSG101 function. Decreased expression of TSG101 is associated with the occurrence of certain human cancers, including breast carcinomas. The TSG101 nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like. The DNA is further used as a diagnostic for a genetic predisposition to cancer, and to identify specific cancers having mutations in this gene.