Determination of HIF-1α degradation pathways via modulation of the propionyl markopen access
- Authors
- Jeong, K.[Jeong, Kwanyoung]; Choi, J.[Choi, Jinmi]; Choi, A.[Choi, Ahrum]; Shim, J.[Shim, Joohee]; Kim, Y.A.[Kim, Young Ah]; Oh, C.[Oh, Changseok]; Youn, H.-D.[Youn, Hong-Duk]; Cho, E.-J.[Cho, Eun-Jung]
- Issue Date
- 30-Apr-2023
- Publisher
- The Biochemical Society of the Republic of Korea
- Keywords
- Chaperone-mediated autophagy; HIF-1α; p300; SIRT1; Ubiquitin-proteasome system
- Citation
- BMB Reports, v.56, no.4, pp.252 - 257
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- BMB Reports
- Volume
- 56
- Number
- 4
- Start Page
- 252
- End Page
- 257
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/105913
- DOI
- 10.5483/BMBRep.2022-0191
- ISSN
- 1976-6696
- Abstract
- The hypoxia-inducible factor-1α (HIF-1α) is a key regulator of hypoxic stress under physiological and pathological conditions. HIF-1α 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-1α proteostasis remain unclear. Here, we found a HIF-1α species propionylated at lysine (K) 709 by p300/CREB binding protein (CBP). HIF-1α stability and the choice of degradation pathway were affected by HIF-1α propionylation. K709-propionylation prevented HIF-1α from degradation through the UPS, while activated chaperon-mediated autophagy (CMA) induced the degradation of propionylated and nonpropionylated HIF-1α. CMA contributed to HIF-1α 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-1α distribution into two different degradation pathways. [BMB Reports 2023; 56(4): 252-257] © 2023 by the The Korean Society for Biochemistry and Molecular Biology
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Pharmacy > Department of Pharmacy > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.