Disclosed is a dTAG system comprising small molecule degraders of mutant BET family protein-tagged proteins via recruitment of an E3 ubiquitin ligase and uses thereof.

Degradation compounds include a cyclic cell penetrating peptide (cCPP) and a degradation construct. The degradation construct includes a degradation moiety and a targeting moiety. The targeting moiety binds a target protein. When the targeting moiety is bound to the target protein, the degradation moiety mediates degradation of the target protein. The cCPP facilitates transfer of the degradation construct into a cell. The degradation compound may further include an exocyclic peptide to enhance endosomal escape of the compound or degradation construct once inside the cell.

Methods of assessing the efficacy of an agent in treating a disease or disorder are provided that include determining whether the agent causes, or inhibits, direct or indirect recruitment and/or ubiquitination and/or degradation of argininosuccinate synthetase 1 (ASS1).

This invention relates to compositions and methods for modifying Homologous to E6AP C-Terminus (HECT) E3 Ubiquitin Protein Ligase (UPL) genes in plants, optionally to improve yield traits. The invention further relates to plants having increased improved yield traits produced using the methods and compositions of the invention.

Described herein are agents that inhibit CBL autoinhibition, agents that activate CBL, SLAP and/or SLAP2 mimetics, and recombinant SLAP and/or SLAP2 or variants and/or fragments thereof that inhibit CBL autoinhibition. Also described are fusion proteins comprising these molecules as well as methods of inhibiting CBL autoinhibition and related uses thereof.

Angelman Syndrome (AS) is a genetic disorder occurring in approximately one in every 15,000 births. It is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. We have generated a Ube3a protein with additional sequences that should allow the secretion from cells and uptake by neighboring neuronal cells. This would confer a functional E6-AP protein into the neurons and rescue disease pathology.

The disclosure relates to methods for treating cancers (e.g., cancers having a BRCA1 and/or BRCA2 mutation(s)) by administering to the subject an effective amount of a ubiquitin-specific protease 1 (USP1) inhibitor.

Methods for the treatment of weight-related disorders, including obesity and disorders associated with obesity, as well as underweight and disorders associated with underweight, by modulating Rlim levels.

An isolated or purified antisense oligomer with a modified backbone structure for modifying pre-mRNA splicing in the parkin gene transcript or part thereof.

Disclosed herein is iCP-mParkin. The iCP-mParkin exhibits biological features suitable for treating neuronal cell damage-related diseases. Thus, the iCP-mParkin provided herein can be used in a composition or method for treating, preventing, or alleviating Parkinson's disease, Alzheimer's disease, and Huntington's disease. Furthermore, the iCP-mParkin is higher in stability than conventional iCP-Parkin and as such, is suitable for use as a protein medicine. In addition, the iCP-mParkin obtained by the preparation method provided herein is of high purity and the preparation method is suitable for mass production.