Abstract: Disclosed are any of the methods or compositions herein. Disclosed are methods of treating a subject having cancer comprising administering a proteasome inhibitor to the subject having cancer, wherein the subject having cancer has a non-functional ATAD1 gene. Disclosed are methods of diagnosing and treating cancer, the method comprising: diagnosing a subject as being susceptible to treatment by a proteasome inhibitor; and administering a proteasome inhibitor to the subject.

Abstract: Disclosed herein are compositions and methods for treating mitochondrial dysfunction. The methods can include compositions capable of increasing or overexpressing ATAD1. The methods include restoring mitochondrial respiration and ATP production. The present disclosure provides a mechanism for peroxin (peroxisomal biogenesis factors) accumulation on mitochondria that affects respiration and ATP generation.

Abstract: Disclosed herein are methods and compositions for the diagnosis and treatment of conditions associated with aberrant pyruvate metabolism, and symptoms thereof, in a subject. Disclosed herein are methods of detecting an aberrant pyruvate metabolism-associated condition, and symptoms thereof, in a subject, by the expression level of MPC1 or MPC2. Disclosed herein are methods of detecting an aberrant pyruvate metabolism-associated condition, and symptoms thereof, in a subject, by the activity level of MPC1 or MPC2. Disclosed herein are methods of determining responsiveness to a treatment for an aberrant pyruvate metabolism associated condition, and symptoms thereof, in a subject.

Abstract: Disclosed herein are methods and compositions for the diagnosis and treatment of conditions associated with aberrant pyruvate metabolism, and symptoms thereof, in a subject. Disclosed herein are methods of detecting an aberrant pyruvate metabolism-associated condition, and symptoms thereof, in a subject, by the expression level of MPC1 or MPC2. Disclosed herein are methods of detecting an aberrant pyruvate metabolism-associated condition, and symptoms thereof, in a subject, by the activity level of MPC1 or MPC2. Disclosed herein are methods of determining responsiveness to a treatment for an aberrant pyruvate metabolism associated condition, and symptoms thereof, in a subject.

Abstract: The present invention is directed towards methods for measuring and assaying PAS Kinase activity. The methods are useful, for example, for detecting PASK activity in a cell, and for screening for small molecule regulators of PAS kinase activity, as well as characterizing endogenous factors and stimuli that modulate PAS kinase activity, and identifying and optimizing the activity of potential PAS kinase inhibitors.

Abstract: The present invention provides methods, compositions, and kits associated with succinate dehydrogenase-related disease conditions. In one aspect of the present invention, a method for screening a test subject to determine risk for developing a succinate dehydrogenase-related disease condition is provided. Such a method can include obtaining a biological sample from the test subject and identifying a mutation in gene hSDH5 from the biological sample of the test subject, wherein the mutation effectuates a decreased level of succinate dehydrogenase flavination in the test subject as compared to a level of succinate dehydrogenase flavination in a normal subject. In one aspect, the mutation is at hSDH5 Gly78 of gene hSDH5. In another aspect, the mutation is equivalent to an hSDH5 Gly78Arg substitution of gene hSDH5.

Abstract: Disclosed are compositions and methods related to PAS Kinase (PASK) and various diseases and disorders associated therewith. Included are methods for treating insulin resistance, cancer, and diabetes comprising administering a composition that inhibits PAS Kinase. Further included are methods, including high throughput screening methods, for identifying test compounds that modulate PAS Kinase.

Abstract: The invention provides methods and compositions relating to a novel kinase designated PAS Kinase (PASK). The compositions include isolated polypeptides comprising a native PASK protein or a PASK N-terminal domain and polypeptides consisting of a PASK PAS-A or PAS-B domain, as well as isolated polynucleotides encoding such polypeptides, and expression vectors and cells comprising such polynucleotides. The methods include binding assays comprising the steps of incubating a mixture comprising a subject polypeptide with a ligand under conditions wherein the polypeptide binds the ligand; and detecting binding of the polypeptide to the ligand.

Abstract: A functional surface binding specificity of a PAS domain, wherein the PAS domain is predetermined, prefolded in its native state, and comprises a hydrophobic core that has no NMR-apparent a priori formed ligand cavity, is changed by (a) introducing into the hydrophobic core of the PAS domain a foreign ligand of the PAS domain; and (b) detecting a change in the functional surface binding specificity of the PAS domain.

Abstract: Specific binding of a foreign core ligand to a PAS domain, wherein the PAS domain is predetermined, prefolded in its native state, and comprises a hydrophobic core that has no NMR-apparent a priori formed ligand cavity, is determined by (a) detecting a first NMR spectrum of the PAS domain in the presence of a foreign ligand; and (b) comparing the first NMR spectrum with a second NMR spectrum of the PAS domain in the absence of the ligand to infer the presence the ligand specifically bound within the hydrophobic core of the PAS domain. A functional surface binding specificity of a PAS domain, wherein the PAS domain is predetermined, prefolded in its native state, and comprises a hydrophobic core that has no NMR-apparent a priori formed ligand cavity, is changed by (a) introducing into the hydrophobic core of the PAS domain a foreign ligand of the PAS domain; and (b) detecting a change in the functional surface binding specificity of the PAS domain.

Abstract: The invention provides methods and compositions relating to a novel kinase designated PAS Kinase (PASK). The compositions include isolated polypeptides comprising a native PASK protein or a PASK N-terminal domain and polypeptides consisting of a PASK PAS-A or PAS-B domain, as well as isolated polynucleotides encoding such polypeptides, and expression vectors and cells comprising such polynucleotides. The methods include binding assays comprising the steps of incubating a mixture comprising a subject polypeptide with a ligand under conditions wherein the polypeptide binds the ligand; and detecting binding of the polypeptide to the ligand.

Abstract: The invention provides methods and compositions relating to a novel kinase designated PAS Kinase (PASK). The compositions include isolated polypeptides comprising a native PASK protein or a PASK N-terminal domain and polypeptides consisting of a PASK PAS-A or PAS-B domain, as well as isolated polynucleotides encoding such polypeptides, and expression vectors and cells comprising such polynucleotides. The methods include binding assays comprising the steps of incubating a mixture comprising a subject polypeptide with a ligand under conditions wherein the polypeptide binds the ligand; and detecting binding of the polypeptide to the ligand.