SIRT1 deacetylates and stabilizes hypoxia-inducible factor-1α (HIF-1α) via direct interactions during hypoxia

Joo, Hyun Jin; Yun, Miyong; Jeong, Jae‐Weon; Park, Eun Ran; Shin, Hyun Jin; Woo, Seon Rang; Jung, Jin Kyu; Kim, Yong Min; Park, Joong Jean; Kim, Joon; Lee, Kee Ho

doi:10.1016/j.bbrc.2015.04.119

Cited by 107 publications

(79 citation statements)

References 24 publications

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“…For example, acetylation of histones promotes gene transcription and a correlation between degree of histone acetylation and tumor aggressiveness has been observed [40]. Further evidence for the importance of acetylation homeostasis in cancer progression comes from the observation that disrupting acetylation dynamics by inhibiting deacetylases (i.e., HDACs, sirtuins) leads to potent induction of cancer cell death [12, 15]. While several aspects of acetylation are being extensively studied, much remains unknown about absolute pool sizes and turnover of acetate bound to bio-molecules in the various cell compartments, let alone how they are affected by tumor-relevant conditions.…”

Section: Resultsmentioning

confidence: 99%

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A rapid method for quantifying free and bound acetate based on alkylation and GC-MS analysis

et al. 2016

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Background: Acetyl-CoA is a key metabolic intermediate with roles in the production of energy and biomass, as well as in metabolic regulation. It was recently found that acetate is crucial for maintaining acetyl-CoA production in hypoxic cancer cells. However, the availability of free acetate in the tumor environment and how much tumor cells consume remains unknown. Similarly, much is still to be learned about changes in the dynamics and distribution of acetylation in response to tumor-relevant conditions. The analysis of acetate is non-trivial, and to help address these topics, we developed a rapid and robust method for the analysis of both free and bound acetate in biological samples.

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Section: Resultsmentioning

confidence: 99%

“…Acetylation is especially prominent on histones and is important for controlling gene expression [11–13]. Based on this, it is not surprising that acetyl-transferases, sirtuins, and histone deacetylases have been found to play important roles in tumorigenesis [14, 15]. …”

Section: Introductionmentioning

confidence: 99%

A rapid method for quantifying free and bound acetate based on alkylation and GC-MS analysis

et al. 2016

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“…Several environmental stresses including hypoxia reduces intracellular NAD + levels in mammalian cells, which results in decreased deacetylase activity of SIRT [34]. SIRT1 is the most studied SIRT family member in gene regulation, but its effect on HIF-1 transcriptional activity is still under debate [34, 63–66]. Dioum et al reported that SIRT1 selectively interacts with HIF-2α and deacetylates HIF-2α to increase its transcriptional activity in human hepatoma Hep3B cells [65].…”

Section: Regulation Of Hif Transcriptional Activity By Epigenetic Eramentioning

confidence: 99%

“…Forced expression of SIRT1 decreases hypoxia-induced expression of PDK1, VEGFA, and CA9, and impairs tumor growth in xenograft mice [34]. Subsequent studies indicate that SIRT1 indirectly acts on HIF-1 transcriptional activity through HIF-1α protein stability [63, 64]. Genetic or pharmacological inhibition of SIRT1 increases the acetylation of HIF-1α to decrease stabilization of HIF-1α protein and HIF-1-dependent gene expression in human cancer cell lines.…”

Section: Regulation Of Hif Transcriptional Activity By Epigenetic Eramentioning

confidence: 99%

Epigenetic regulators: multifunctional proteins modulating hypoxia-inducible factor-α protein stability and activity

Luo

Wang

2017

Cell. Mol. Life Sci.

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The hypoxia-inducible factor (HIF) is a heterodimeric transcription factor governing a transcriptional program in response to reduced O2 availability in metazoans. It contributes to physiology and pathogenesis of many human diseases through its downstream target genes. Emerging studies have shown that the transcriptional activity of HIF is highly regulated at multiple levels and the epigenetic regulators are essential for HIF-mediated transactivation. In this review, we will discuss the comprehensive regulation of HIF transcriptional activity by different types of epigenetic regulators.

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“…The effect of phosphorylation on the stability of HIF-1α depends on the kinase involved [18,19]; it has been reported that HIF-1α is destabilized by GSK-3β [20] and PLK3 [21], but stabilized by CDK1 [22] and ATM [23]. The reversal of these PTMs, such as deubiquitination [24], deSUMOylation [25], deacetylation [26,27], and demethylation [17], also regulates HIF-1α stability. As for phosphatase regulating HIF-1α, SHP-1 decreases HIF-1α’s expression although direct dephosphorylation of HIF-1α by SHP-1 has not been determined [28].…”

Section: Introductionmentioning

confidence: 99%

The Protein Phosphatase PPM1G Destabilizes HIF-1α Expression

Pyo

Ryu

Kim

et al. 2018

IJMS

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Hypoxia-inducible factors (HIFs) are key regulators of hypoxic responses, and their stability and transcriptional activity are controlled by several kinases. However, the regulation of HIF by protein phosphatases has not been thoroughly investigated. Here, we found that overexpression of Mg2+/Mn2+-dependent protein phosphatase 1 gamma (PPM1G), one of Ser/Thr protein phosphatases, downregulated protein expression of ectopic HIF-1α under normoxic or acute hypoxic conditions. In addition, the deficiency of PPM1G upregulated protein expression of endogenous HIF-1α under normoxic or acute oxidative stress conditions. PPM1G decreased expression of HIF-1α via the proteasomal pathway. PPM1G-mediated HIF-1α degradation was dependent on prolyl hydroxylase (PHD), but independent of von Hippel-Lindau (VHL). These data suggest that PPM1G is critical for the control of HIF-1α-dependent responses.

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SIRT1 deacetylates and stabilizes hypoxia-inducible factor-1α (HIF-1α) via direct interactions during hypoxia

Cited by 107 publications

References 24 publications

A rapid method for quantifying free and bound acetate based on alkylation and GC-MS analysis

A rapid method for quantifying free and bound acetate based on alkylation and GC-MS analysis

Epigenetic regulators: multifunctional proteins modulating hypoxia-inducible factor-α protein stability and activity

The Protein Phosphatase PPM1G Destabilizes HIF-1α Expression

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