Determination of HIF-1α degradation pathways via modulation of the propionyl mark
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The hypoxia-inducible factor-1α (HIF-1α) is a key regulator ofhypoxic stress under physiological and pathological conditions. HIF-1α protein stability is tightly regulated by the ubiquitin-proteasomesystem (UPS) and autophagy in normoxia, hypoxia,and the tumor environment to mediate the hypoxic response. However, the mechanisms of how the UPS and autophagy interplayfor HIF-1α proteostasis remain unclear. Here, we founda HIF-1α species propionylated at lysine (K) 709 by p300/CREBbinding protein (CBP). HIF-1α stability and the choice of degradationpathway were affected by HIF-1α propionylation. K709-propionylation prevented HIF-1α from degradation throughthe UPS, while activated chaperon-mediated autophagy (CMA)induced the degradation of propionylated and nonpropionylatedHIF-1α. CMA contributed to HIF-1α degradation in both normoxiaand hypoxia. Furthermore, the pan-cancer analysis showedthat CMA had a significant positive correlation with the hypoxicsignatures, whereas SIRT1, responsible for K709-depropionylationcorrelated negatively with them. Altogether, our results revealeda novel mechanism of HIF-1α distribution into two differentdegradation pathways.
Abstract
The hypoxia-inducible factor-1α (HIF-1α) is a key regulator ofhypoxic stress under physiological and pathological conditions. HIF-1α protein stability is tightly regulated by the ubiquitin-proteasomesystem (UPS) and autophagy in normoxia, hypoxia,and the tumor environment to mediate the hypoxic response. However, the mechanisms of how the UPS and autophagy interplayfor HIF-1α proteostasis remain unclear. Here, we founda HIF-1α species propionylated at lysine (K) 709 by p300/CREBbinding protein (CBP). HIF-1α stability and the choice of degradationpathway were affected by HIF-1α propionylation. K709-propionylation prevented HIF-1α from degradation throughthe UPS, while activated chaperon-mediated autophagy (CMA)induced the degradation of propionylated and nonpropionylatedHIF-1α. CMA contributed to HIF-1α degradation in both normoxiaand hypoxia. Furthermore, the pan-cancer analysis showedthat CMA had a significant positive correlation with the hypoxicsignatures, whereas SIRT1, responsible for K709-depropionylationcorrelated negatively with them. Altogether, our results revealeda novel mechanism of HIF-1α distribution into two differentdegradation pathways.
참고문헌 (36)
- Wang GL, "Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension", Proc Natl Acad Sci U S A, 92, pp.5510~5514 (1995)
- Arany Z, "An essential role for p300", CBP in the cellular response to hypoxia, 1996, pp.93, 12969~12973
- Semenza GL, "Hypoxia-inducible factor 1 : oxygen homeostasis and disease pathophysiology", Trends Mol Med, 7, pp.345~350 (2001)
- 홍순선, "HIF-1alpha: a Valid Therapeutic Target for Tumor Therapy", Cancer Research and Treatment, 36(6), pp.343~353 (2004), 대한암학회
- Dengler VL, "Transcriptional regulation by hypoxia inducible factors", Crit Rev Biochem Mol Biol, 49, pp.1~15 (2014)
- Epstein ACR, "Celegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation", Cell, 107, pp.43~54 (2001)
- Ivan M, "HIF alpha targeted for VHL-mediated destruction by proline hydroxylation : Implications for O-2 sensing", Science, 292, pp.464~468 (2001)
- Maxwell PH, "The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis", Nature, 399, pp.271~275 (1999)
- Cockman ME, "Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein", J Biol Chem, 275, pp.25733~25741 (2000)
- Boya P, "Emerging regulation and functions of autophagy", Nat Cell Biol, 15, pp.713~720 (2013)
- Mizushima N, "A brief history of autophagy from cell biology to physiology and disease", Nat Cell Biol, 20, pp.521~527 (2018)
- Kaushik S, "The coming of age of chaperone-mediated autophagy", Nat Rev Mol Cell Biol, 19, pp.365~381 (2018)
- Hubbi ME, "Chaperone-mediated autophagy targets hypoxia-inducible factor-1 alpha(HIF-1 alpha)for lysosomal degradation", J Biol Chem, 288, pp.10703~10714 (2013)
- Ferreira JV, "STUB1", CHIP is required for HIF1A degradation by chaperone-mediated autophagy, 2013, pp.9, 1349~1366
- Ferreira JV, "K63 linked ubiquitin chain formation is a signal for HIF1A degradation by chaperone-mediated autophagy", Sci Rep, 5, pp.10210~ (2015)
- Prabakaran S, "Post-translational modification : nature’s escape from genetic imprisonment and the basis for dynamic information encoding", Wiley Interdiscip Rev Syst Biol Med, 4, pp.565~583 (2012)
- Kebede AF, "Histone propionylation is a mark of active chromatin", Nat Struct Mol Biol, 24, pp.1048~1056 (2017)
- Sabari BR, "Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation", Mol Cell, 58, pp.203~215 (2015)
- Geng H, "HIF1 alpha protein stability is increased by acetylation at lysine 709", J Biol Chem, 287, pp.35496~35505 (2012)
- Lim JH, "Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1 alpha", Mol Cell, 38, pp.864~878 (2010)
- Ghosh R, "Chaperone-mediated autophagy protects cardiomyocytes against hypoxic-cell death", Am J Physiol Cell Physiol, 323, pp.1555~1575 (2022)
- Dohi E, "Hypoxic stress activates chaperone-mediated autophagy and modulates neuronal cell survival", Neurochem Int, 60, pp.431~442 (2012)
- Finkel T, "Recent progress in the biology and physiology of sirtuins", Nature, 460, pp.587~591 (2009)
- Houtkooper RH, "Sirtuins as regulators of metabolism and healthspan", Nat Rev Mol Cell Biol, 13, pp.225~238 (2012)
- Jeong JW, "Regulation and destabilization of HIF-1 alpha by ARD1-mediated acetylation", Cell, 111, pp.709~720 (2002)
- Kim Y, "Methylation-dependent regulation of HIF-1 alpha stability restricts retinal and tumour angiogenesis", Nat Commun, 7, pp.10347~ (2016)
- Fluegel D, "Glycogen synthase kinase 3 phosphorylates hypoxiainducible factor 1 alpha and mediates its destabilization in a VHL-independent manner", Mol Cell Biol, 27, pp.3253~3265 (2007)
- Wang XJ, "A novel crosstalk between two major protein degradation systems Regulation of proteasomal activity by autophagy", Autophagy, 9, pp.1500~1508 (2013)
- Seo KS, "SIRT2 regulates tumour hypoxia response by promoting HIF-1α hydroxylation", Oncogene, 34, pp.1354~1362 (2015)
- Tomita T, "Sirt1-deficiency causes defective protein quality control", Sci Rep, 5, pp.12613~ (2015)
- Joshi S, "MDM2 regulates hypoxic hypoxia-inducible factor 1 alpha stability in an e3 ligase, proteasome, and PTEN-phosphatidylinositol 3-kinase-AKT-dependent manner", J Biol Chem, 289, pp.22785~22797 (2014)
- Simithy J, "Characterization of histone acylations links chromatin modifications with metabolism", Nat Commun, 8, pp.1141~ (2017)
- Furuta E, "Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt and sterol regulatory element binding protein-1", Cancer Res, 68, pp.1003~1011 (2008)
- Bensaad K, "Fatty acid uptake and lipid storage induced by HIF-1 alpha contribute to cell growth and survival after hypoxia-reoxygenation", Cell Rep, 9, pp.349~365 (2014)
- Schug ZT, "Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress", Cancer Cell, 27, pp.57~71 (2015)
- Trefely S, "Quantitative subcellular acyl-CoA analysis reveals distinct nuclear metabolism and isoleucine-dependent histone propionylation", Mol Cell, 82, pp.447~462 (2022)