Ubiquitin-Like Proteins: Regulation and function

Protein degradation via the Ubiquitin Proteasome System (UPS) is highly selective and regulated process. The UPS serves as a quality-control mechanism that rapidly eliminates aberrant proteins whose accumulation would interfere with normal cell function and viability as well as playing a regulatory process by controlling key cellular pathways. In most cases, substrates targeted for destruction in the UPS are conjugated to Ubiquitin (Ub) molecules, a process known as ubiquitination. Over the years, several Ub-like (UBL) proteins were identified and have been shown to regulate diverse cellular functions. Here, we investigate the regulation and substrate specificity of UBL proteins, focusing on how UBLs regulate protein turnover. To identify substrates of UBL proteins, we generated by CRISPR/Cas9 approach knock out cell lines for various UBLs followed by substrate identification using proteomic approaches. To characterize the regulation of UBLs, protein-protein interactions via IP-mass spectrometry are being explored. Better understanding of UBL regulation and function will help us to expand our knowledge of the cross talk between the UBL proteins in controlling and filtering the proteome.