High levels of nuclear NMT1 are associated with longer relapse free survival in ERα positive breast cancer patients. Both low levels of cytosolic and nuclear NMT1 correlated to very poor clinical outcomes. NMT2 also plays an important function in breast cancer signalling, regulated through phosphorylation. For example, NMT2 phosphorylation status is a key element in the progression of ER+ breast cancer cells. Specifically, nuclear localization of NMT2 is associated with poor outcomes in breast cancer patients.

The present application provides a method of assaying pyruvate dehydrogenase complex (PDHC) activity in a mammalian cell that expresses human sirtuin 4 (SIRT4) comprising measuring a level of a dihydrolipoyllysine acetyltransferase (DLAT) lipoamide peptide comprising the amino acid sequence TDK[lipoyl]AT in the cell. The present application also demonstrates that sirtuin 4 (SIRT4) acts as a cellular lipoamidase that negatively regulates pyruvate dehydrogenase complex (PDHC) activity through hydrolysis of its lipoamide cofactors.

The present invention relates to Abhydrolase containing domain 5 (ABHD5) and N-terminal fragments of HDAC4 (HDAC4-NT) and variants of the aforementioned peptides for the treatment and prevention of heart failure. The present invention further provides vectors for the cardiomyocyte-specific expression of said peptides and a test system comprising ABHD5 for the identification of novel compounds which are useful for the treatment of heart failure.

Provided herein are turn-on fluorescent chemical probes useful for monitoring and/or detecting lysine delipoylation activity in a sample including or suspected of including a delipoylation enzyme.

Among the various aspects of the present disclosure is the provision of a method of detection, treatment, and monitoring of cardiovascular disease or a foot wound by detection of a novel biomarker, Fatty Acid Synthase (FAS). Briefly, therefore, the present disclosure is directed to methods that allow for improved, noninvasive, and reliable diagnosis of these conditions, particularly in subjects suffering from Type 2 Diabetes (T2D).

Described herein is the Identification of the NMT isozyme overexpressed in PBMCs of colorectal cancer patients and the cell types overexpressing NMT2 in the PBMCs of CRC patients.

Described herein are compounds, compositions and methods for treatment of cancer. Also described are methods and uses for identifying subject with cancer that are suitable for treatment with the compounds, composition and methods are described herein.

The present invention relates to compositions and methods for inhibiting DHHC3 palmitoyltransferase for treating cancer. Described herein, are methods of inhibiting expression or activity of programmed death-ligand 1 (PD-L1) in a cell of a subject, e.g., a human subject, in need thereof are carried out by administering to the subject an effective amount of a palmitoyltransferase inhibitor, thereby inhibiting the expression or activity of PD-L1 in the subject. The palmitoyltransferase comprises an Asp-His-His-Cys motif (DHHC)-type protein. Exemplary DHHC-type proteins include DHHC3, DHHC5, DHHC7, and DHHC17.

The present invention relates to Abhydrolase containing domain 5 (ABHD5) and N-terminal fragments of HDAC4 (HDAC4-NT) and variants of the aforementioned peptides for the treatment and prevention of heart failure. The present invention further provides vectors for the cardiomyocyte-specific expression of said peptides and a test system comprising ABHD5 for the identification of novel compounds which are useful for the treatment of heart failure.

Provided herein are methods and compositions for the treating a patient with one or more conditions associated with PNPLA3, such as nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and/or alcoholic liver disease (ALD). Methods and compositions are also provided for modulating the expression of the PNPLA3 gene in a cell by altering gene signaling networks. Companion diagnostic methods, compositions and kits are also provided.