Abstract: Disclosed are methods and compositions for the identification, characterization and inhibition of farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21ras. One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. The enzyme appears to comprise one or two subunits of approximately 50 kDa each. Methods are disclosed for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21ras. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme.

Abstract: Disclosed are methods and compositions for the identification, characterization and inhibition of farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21ras. One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. The enzyme appears to comprise one or two subunits of approximately 50 kDa each. Methods are disclosed for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21ras. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme.

Abstract: The invention provides assays for the identification of modulators of Site-1 protease. Further provided by the invention are expression constructs and the transgenic cells useful for the development of such assays for Site-1 specific protease. The cells allow the implementation of in vitro assays for potential modulators of Site-specific proteases. Still further provided by the invention are in vitro assays employing Site-1 protease which has been isolated from cells.

Abstract: Disclosed are methods and compositions for the identification, characterization and inhibition of mammalian protein farnesyltransferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21.sup.ras. One protein farnesyltransferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. Also disclosed are methods and compositions for the preparation of farnesyltransferase by recombinant means, following the molecular cloning and co-expression of its two subunits, for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21.sup.ras.

Abstract: Disclosed are methods and compositions for the identification, characterization and inhibition of mammalian farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21.sup.ras. The nucleotide and amino acid sequences of the .alpha. and .beta. subunits of both rat and human farnesyl transferase are disclosed, as are methods and compositions for the preparation of farnesyl transferase by recombinant means, following the molecular cloning and co-expression of its two subunits, for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21.sup.ras. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme.

Abstract: Disclosed are methods and compositions for the identification of inhibitors of farnesyltransferase enzymes involved in the prenylation of various cellular proteins, including cancer related ras proteins, such as p21.sup.ras, particularly, K-rasB. Enclosed are procedures for using purified farnesyltransferase enzymes and K-rasB proteins in screening protocols for the identification of possible anticancer agents that inhibit the enzyme and thereby prevent prenylation of proteins such as K-RasB.

Abstract: A sterol regulatory element (SRE) binding protein (SREBP) which activates transcription from SREs, such as SRE-1 of the low intensity lipoprotein (LDL) receptor gene, is disclosed, as are DNA segments encoding SREBPs such as an SREBP-1 or SREBP-2. Also described are methods for using SREBP to promote SRE-mediated transcription and LDL receptor production in the presence of sterols, and screening assay for the identification of further agents with such properties. The SREBP and other agents may be used to reduce plasma cholesterol levels and to treat various medical problems associated with hypercholesterolemia.

Abstract: Benzodiazepine derivatives represented by the structure below are disclosed that act as potent inhibitors of ras farnesyl:protein transferase. Pharmaceutical compositions containing these benzodiazepines are provided for treatment of diseases foe which inhibition of the ras farnesyl:protein transferase as indicated.

Abstract: Benzodiazepine derivatives are disclosed that act as potent inhibitors of ras farnesyl:protein transferase. Pharmaceutical compositions containing these benzodiazepines are provided for treatment of diseases for which inhibition of the ras farnesyl:protein transferase is indicated.

Abstract: A sterol regulatory element (SRE) binding protein (SREBP) which activates transcription from SREs, such as SRE-1 of the low density lipoprotein (LDL) receptor gene, is disclosed, as are DNA segments encoding SREBPs such as an SREBP-1 or SREBP-2. Also described are methods for using SREBP to promote SRE-mediated transcription and LDL receptor production in the presence of sterols, and screening assay for the identification of further agents with such properties. The SREBP and other agents may be used to reduce plasma cholesterol levels and to treat various medical problems associated with hypercholesterolemia.

Abstract: A nuclear protein which binds sterol regulatory elements (SREs), such as SRE-1 of the low density lipoprotein (LDL) receptor gene, and mediates sterol-regulated transcription of the LDL receptor gene is disclosed. Also described are screening assay and methods for the identification of agents capable of promoting LDL receptor gene transcription for use in reducing plasma cholesterol and treating the various medical problems associated therewith.

Abstract: Disclosed are methods and compositions for the identification, characterization and inhibition of mammalian farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21.sup.ras. One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. Also disclosed are methods and compositions for the preparation of farnesyl transferase by recombinant means, following the molecular cloning and co-expression of its two subunits, for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21.sup.ras.

Abstract: Disclosed are discreet functionally translocatable DNA segments, termed Sterol Regulatory Elements (SRE's) , which are fused to heterologous structural genes to provide sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeats 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discreet sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes.

Abstract: Disclosed are discrete functionally translocatable DNA segments, termed Sterol Regulatory Elements (SREs), which are fused to heterologous structural genes to provide sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeat 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discrete sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes.

Abstract: Disclosed are discreet functionally translocatable DNA segments, termed Sterol Regulatory Elements (SRE's), which are fused to heterologous structural genes to provide sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeat 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discreet sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes.

Abstract: Disclosed are methods and compositions for the identification, characterization and inhibition of farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21.sup.ras. One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. The enzyme appears to comprise one or two subunits of approximately 50 kDa each. Methods are disclosed for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21.sup.ras. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme.

Abstract: Recombinant DNA transfer vectors containing DNA inserts which are complementary to either the human LDL receptor gene, or its mRNA transcript, are disclosed. Also disclosed are methods which utilize these genetic probes for diagnosing Familial Hypercholesterolemia (FH) in a suspected individual. A case study of numerous such individual are disclosed wherein the genetic deletion mutation is detailed with great precision through the practice of this invention.

Abstract: Disclosed are discreet functionally translocatable DNA segments, termined Sterol Regulatory Elements (SRE's), which are fused to heterologous structural genes to provided sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeat 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discreet sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes.

Abstract: Recombinant DNA transfer vectors containing DNA inserts which are complementary to either the human LDL receptor gene, or its mRNA transcript, are disclosed. Also disclosed are methods which utilize these genetic probes for diagnosing Familial Hypercholesterolemia (FH) in a suspected individual. A case study of one such individual, FH 274, is disclosed wherein the genetic deletion mutation is detailed with great precision through the practice of this invention.