When all goes according to plan, newly synthesized proteins within cells fold down an energetic funnel into a functional, minimal energy configuration. If a protein does not fold properly, it is both energetically unfavorable and nonfunctional, often with hydrophobic parts exposed to the aqueous environment. This creates the potential for misfolded proteins to form insoluble aggregates, which can become toxic to cells. These aggregates can crowd the cellular environment and impair cellular functions, which on a single cell scale can lead to cell death and on a larger organism scale, cause diseases like Alzheimer’s, Parkinson’s, and Huntington’s. To deal with this problem, cells have evolved protein quality control (PQC) systems that comprise two classes of action: chaperones that help proteins fold properly and ubiquitin-protein ligases that tag misfolded proteins with ubiquitin for destruction by the proteasome. Previous studies concluded that chaperones are required protein degradation. In our study, we find that Hsp70 chaperone dependence for protein degradation is variable along a spectrum of independent to dependent. My work specifically examined the function of yeast ubiquitin-protein ligase San1 by comparing degradation of various substrates between strains with or without San1 function, and with or without chaperone activity. By performing degradation whereby protein synthesis was halted and the stability of the synthesized pool of substrate was monitored by Western analyses, we were able to see the degree of substrate degradation by each strain over time. Degradation through San1 has been shown to require chaperones, but San1 also is known to recognize substrates independently without chaperones. From our work, San1 recognizes patches of hydrophobicity on misfolded proteins; a feature that is also recognized by chaperones. By studying the interactions of the folding and degradation enzymes, we are gaining a new understanding of how PQC pathways collaborate and coordinate to achieve optimal protection for the cell.