The invention relates to UBE3A protein targets and their usage as target engagement biomarkers for compounds that modulate ube3a expression.

Provided herein are methods of detecting binding of an SENP1 polypeptide to a compound and methods for screening for inhibitors of SENP1. Further provided are aqueous compositions comprising SENP1 polypeptides and NMR apparatuses comprising the compositions for NMR analysis.

Provided herein is technology relating to the biological process of protein ubiquitination and particularly, but not exclusively, to compositions and methods for studying protein ubiquitination and developing therapeutics to modulate protein ubiquitination.

Disclosed is a recombinant protein composed by the fusion of Glutathione S-transferase (GST), or an esa-histidine peptide (poly-His), or Maltose Binding Protein (MBP), to the Carboxyl-terminus end of the human KHNYN protein, containing residues 597-678 or a region including at least the amino acidic region 630-678. Also disclosed is a second recombinant protein where the Carboxyl-terminus end of the human KHNYN protein, containing residues 627-678 is genetically fused in a tandem construct to the Carboxyl-terminus end of KHNYN including residues 597-678. The tandem construct is N-terminally tagged with Glutathione S-transferase (GST), or an esa-histidine peptide (poly-His), or Maltose Binding Protein (MBP). The potential use of these Neddylation sensors also called Neddylation probes to isolate mono-, poly-neddylated targets as well as substrates modified by the addition of ubiquitin-NEDD8 mixed chains is considered.

The present invention relates to the identification and use of biomarkers for the diagnosis and prognosis of cancer.

The invention provides antibodies that bind mixed-topology polyubiquitin and multispecific anti-polyubiquitin antibodies, and methods of using the same.

The invention provides anti-polyubiquitin antibodies and methods of using the same.

Provided herein and methods and kits for identifying inhibitors of SUMOylation. The provided methods include contacting a candidate agent with (i) a SUMO-conjugating peptide comprising an N-terminal linker and a detectable tag, and (ii) a SUMO comprising a metal complex, under conditions that allow binding between the SUMO-conjugating peptide and the SUMO, and detecting the detectable tag thereby determining the level of binding between the SUMO-conjugating peptide and SUMO. A reduced level of binding as compared to the level of binding in the absence of the candidate agent indicating the agent inhibits SUMOylation.

Deubiquitinating enzyme (DUB) probes are provided that resemble native diubiquitin (diUB) with a similar linkage size and that may contain a Michael acceptor for trapping the DUB active-site cysteine. For example, both K63- and K48-linked diubiquitin probes are generated using a facile chemical ligation method, utilizing the linker compound 3-(2-(bromomethyl)-1,3-dioxolan-2-yl)prop-2-en-1-amine. The diUb probes are capable of labelling DUBs from different families and may be employed to reveal intrinsic linkage specificities of DUBs.

There is described a method for analyzing ubiquitin polymers using linkage-specific deubiquitinase enzymes. Novel specificities of deubiquitinase enzymes are also provided.