The NAPSTR Element: A Novel Pathway for Protein Quality Control

The process of Protein Quality Control (PQC) is necessary for cells to maintain protein homeostasis. This process is complex; cells must differentiate the functioning proteins from the damaged and then decide who is worth saving and who must be destroyed. Within the nuclear complex, failure for PQC to manage aberrant proteins contributes to diseases such as Parkinson’s, Huntington’s and Alzheimer’s. The first nuclear localized PQC pathway identified in Saccharomyces cerevisiae is characterized by SAN1. This gene transcribes San1 ubiquitin ligase that is tasked with targeting aberrant proteins for proteasome degradation. It has been observed that when the SAN1 pathway is hindered cells undergo a Nuclear Aberrant Protein Stress Response (NAPSTR). Our lab is seeking the genetic elements that are responsible for this process. The Heat Shock Protein, HSP26, has been associated with NAPSTR through its promoter, for it becomes upregulated when SAN1 is knocked out. To discover the NAPSTR element in this promoter we will systematically delete segments of the promoter and monitor the transcription of the Hsp26. We expect that when the NAPSTR element is knocked out, transcription of Hsp26 will be stopped. Once the promoter element has been identified we will use bioinformatics to search for homologous regions in the yeast genome to identify NAPSTR elements at additional loci. By understanding the mechanisms of nuclear PQC we will gain essential tools that can be used to combat diseases caused by irregular protein activity.