Determination of HIF-1? degradation pathways via modulation of the propionyl mark.

The hypoxia-inducible factor-1? (HIF-1?) is a key regulator of hypoxic stress under physiological and pathological conditions. HIF-1? protein stability is tightly regulated by the ubiquitin-proteasome system (UPS) and autophagy in normoxia, hypoxia, and the tumor environment to mediate the hypoxic response. However, the mechanisms of how the UPS and autophagy ...
interplay for HIF-1? proteostasis remain unclear. Here, we found a HIF-1? species propionylated at lysine (K) 709 by p300/CREB binding protein (CBP). HIF-1? stability and the choice of degradation pathway were affected by HIF-1? propionylation. K709-propionylation prevented HIF-1? from degradation through the UPS, while activated chaperon-mediated autophagy (CMA) induced the degradation of propionylated and nonpropionylated HIF-1?. CMA contributed to HIF-1? degradation in both normoxia and hypoxia. Furthermore, the pan-cancer analysis showed that CMA had a significant positive correlation with the hypoxic signatures, whereas SIRT1, responsible for K709-depropionylation correlated negatively with them. Altogether, our results revealed a novel mechanism of HIF-1? distribution into two different degradation pathways. [BMB Reports 2023; 56(4): 252-257].
Mesh Terms:
Cell Hypoxia, Humans, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit, Neoplasms, Proteasome Endopeptidase Complex
BMB Rep
Date: Apr. 01, 2023
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