Mutant mono ADP-ribose-polymerases (mono-PARP) proteins and small molecule compound substrates specific for the mutant mono-PARP proteins as well as methods of using these compositions to identify protein targets of the mono-PARPs and to screen for antagonists of the mono-PARPs are described.

The present invention provides an approach for the determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, expression markers and other criteria, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of modulators of cellular activation allows for characterization of pathways and cell populations.

The invention provides methods and compositions for enhancing the efficacy of cancer therapies through modulation of BAL1 and/or BBAP. Also provided are methods for predicting the efficacy of cancer therapies or treating cancer in a subject through modulation of BAL1 and/or BBAP. Further provided are methods for identifying compounds that are capable of modulating BAL1-BBAP complexes.

Poly(ADP-ribose) (PAR) is a protein implicated in numerous neurodegenerative disease states including Parkinson's disease (PD). To date, no routine laboratory test has been developed to diagnosis, assess or monitor patients suffering from PD. Disclosed herein a novel method to assess the PAR concentration in the cerebral spinal fluid (CSF) of a patient and correlate that concentration to the medical condition of a patient with PD. Also disclosed is the use of PAR as a biomarker for PD.

The present invention provides methods of selectively killing a cell, comprising contacting the cell with an agent that inhibits phospho-ribosyl pyrophophosphate synthetase 2 (PRPS2). The present invention also provides methods of identifying a candidate agent that selectively kills neoplastic cells that are Myc-hyperactivated via inhibition of PRPS2.

A radical departure from the classical E1-E2-E3 three-enzyme mediated ubiquitination of eukaryotes, the bacterial enzymes of the SidE family of Legionella pneumophila effectors utilize NAD.sup.+ to ligate ubiquitin onto target substrate proteins achieved via a two-step mechanism involving (1) ADP-ribosylation of ubiquitin followed by (2) phosphotransfer to a target serine residue. Using fluorescent NAD.sup.+ analogues as well as synthetic substrate mimics, a continuous assay system enabling real-time monitoring of both steps of this mechanism is disclosed herein. These assays are amenable to biochemical studies and high-throughput screening of inhibitors of these effectors, and enable the discovery and characterization of putative enzymes similar to the SidE family in other organisms. A kit of the assay system, for real-time monitoring protein ubiquitination and/or identifying an inhibitor for protein ubiquitination comprising a fluorescent NAD+ analogue and a synthetic substrate mimic, is also in the scope of this disclosure.

This invention relates to the finding that FAMIN (fatty acid metabolism-immunity nexus; LACC1, C13orf31)) is a trifunctional purine salvage enzyme that displays a unique combination of adenosine deaminase, purine nucleoside phosphorylase and methylthioadenosine phosphorylase activities. Methods of measuring FAMIN activity and screening for FAMIN modulators are provided that comprise determining the adenosine deaminase activity, purine nucleoside phosphorylase activity and/or methylthioadenosine phosphorylase activity of an isolated FAMIN protein.

This invention relates to the finding that inhibition or inactivation of FAMIN (‘fatty acid metabolism-immunity nexus’; C13orf31; LACC1 (laccase domain containing 1)) reduces tumourigenesis and stimulates cell-mediated immune responses. Method of treating cancer or stimulating cell-mediated immune responses in an individual by reducing FAMIN activity in the individual are provided. Also provided are methods of activating T cells in vitro using FAMIN deficient immune cells and stimulating cell-mediated immune responses comprising administering (a) a population of FAMIN deficient immune cells; or (b) a population of T cells activated in vitro by a population of FAMIN deficient immune cells.

It is an aim of the present invention to provide inhibitors of human diphtheria toxin-like ADP-ribosyltransferases, such as ARTD10, for use as a medicine. It is another aim of the invention to provide compounds for use as human mono-ADP-ribosyltransferase (mARTD) inhibitors in vitro. In the present invention, it has been discovered that human ARTD10, which belongs to an enzyme family linked to cancer biology, can be specifically inhibited by the benzamide comprising compounds disclosed in the invention, such as 4,4′-oxydibenzamide.

The present disclosure relates to compounds of Formula I and II, wherein R.sup.1-R.sup.20 and FL are defined herein. Also provided are methods of targeting alpha-radiation to poly(ADP-ribose)polymerase 1 (PARP-1) enzyme expression, reducing proliferation of cancer cells, reducing proliferation of cancer cells, detecting intact and enzymatically active poly(ADP-ribose)polymerase 1 (PARP-1) enzyme expression, detecting PARP-1 enzyme expression in a subjects tissue sample, monitoring cancer treatment in a subject, or detecting a PARP-1 receptive cancer in a subject. ##STR00001##