Authors:

Anya Jolee Piarowski

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As a heterodimeric transcription factor in charge of keeping cells healthy in hypoxic conditions, Hypoxia inducible factor 1 (HIF1) is critical for many processes within the cell. HIF1a is the alpha subunit of the HIF1 and is degraded when oxygen levels are normal to regulate HIF1 activity, as overactive or underactive HIF1 protein is linked to cardiovascular diseases, cancer, and diabetes. This degradation under normoxic conditions is through a ubiquitination process involving CRL2VHL ubiquitin ligase. Previous works have reported HIF1a can be degraded when CRL2s are inhibited, suggesting a CRL2VHL-independent mechanism for its degradation. In my project, I am using TurboID, a proximity labeling technique, to find protein candidates for this pathway by biotinylating proteins nearby HIF1a. The Oxygen-Dependent Domain (ODD) isolated from HIF1a has been known to be primarily degraded through the CRL2VHL-dependent degradation pathway. Therefore, we can use a cell line that expresses ODD only as a negative control, and ODD will capture proteins responsible for CRL2VHL-dependent pathway or unrelated background proteins. Through comparing results from HIF1a and ODD, I am expecting to get candidate proteins for the CRL2VHL-independent degradation pathway. Later, further experiments can be performed to confirm each protein's role in the CRL2VHL- independent HIF1a degradation. Keywords: HIF1a; ODD; TurboID; Ubiquitination; Degradation

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Purdue University / 2025

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Co-authors:

Anya Jolee Piarowski