Regulation of protein homeostasis in aneuploid cancer cells

• Applicant: Dr. Prince Saforo Amponsah
• Subject Area: Cell Biology ; General Genetics and Functional Genome Biology ; Biochemistry
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 510268075

The proposed project aims to understand the role of p62 (Sequestosome 1 or SQSTM1) in protein homeostasis regulation in aneuploid human cancer cells. The multifunctional protein p62 sequesters damaged proteins and cellular components into cytoplasmic condensates and acts as a shuttle for cargoes destined for degradation. Autophagosomes and proteasomes serve as the two main machineries by which p62-dependent protein homeostasis is achieved in cells. Through proteomic analysis, mitochondrial proteins were identified as the major cargoes of p62 in established aneuploid cell lines. We intend to validate the top identified cargoes of p62 via computational sequence analysis, directed mutagenesis and co-immunoprecipitation assays. We will examine the specific relationship between p62 and protein homeostasis in aneuploidy and mechanistically establish a role for p62 in mitochondrial turnover in aneuploid cells. We will delineate the p62-directed protein degradation flow in aneuploidy by analyzing and comparing the autophagosomal contents as well as proteasome destinated cargoes of p62 in aneuploid cells. The contributions of each of the degradation machineries, autophagosome and proteosome, to protein homeostasis regulation in aneuploidy would be elucidated.

• DFG Programme: WBP Position