Interaction between HIF‐1α (ODD) and hARD1 does not induce acetylation and destabilization of HIF‐1α

Arnesen, Thomas; Kong, Xianguo; Evjenth, Rune; Gromyko, Darina; Varhaug, Jan Erik; Zhao, Lin; Sang, Nianli; Caro, Jaime; Lillehaug, Johan R.

doi:10.1016/j.febslet.2005.10.036

Cited by 82 publications

(74 citation statements)

References 26 publications

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“…GST, glutathione-S-transferase; HBx, HBV regulatory protein; HIF-1a, hypoxia-inducible factor-1a; ODD, oxygen-dependent degradation; WT, wild type. Jeong et al, 2002;Qian et al, 2006), the acetylation hypothesis remains controversial since human ARD1 does not, at least directly, acetylate HIF1a (Arnesen et al, 2005;Bilton et al, 2005Bilton et al, , 2006Fisher et al, 2005;Murray-Rust et al, 2006). Instead, diverse other mechanisms have been proposed for the HDAC inhibitor-induced HIF-1 regulation; Kong et al (2006) showed that HDAC inhibitors induced the proteasomal degradation of HIF-1a by interacting with HSP70 and thereby disrupted the HSP70/HSP90 axis function.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus X protein induces the expression of MTA1 and HDAC1, which enhances hypoxia signaling in hepatocellular carcinoma cells

et al. 2008

Oncogene

142

129

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Expression level of metastasis-associated protein 1 (MTA1) is closely related to tumor growth and metastasis in various cancers. Although increased expression level of MTA1 was observed in hepatocellular carcinoma (HCC), role of MTA1 complex containing histone deacetylase (HDAC) in hepatitis B virus (HBV)-associated hepatocarcinogenesis has not been studied. Here, we demonstrated that HBx strongly induced the expression of MTA1 and HDAC1 genes at transcription level. MTA1 and HDAC1/2 physically associated with hypoxia-inducible factor-1a (HIF-1a) in vivo in the presence of HBx, which was abolished by knockdown of MTA1 by short interfering RNA (siRNA). HBx induced deacetylation of the oxygen-dependent degradation domain of HIF-1a, which was accompanied with dissociation of prolyl hydroxylases and von Hippel-Lindau tumor suppressor from HIF-1a. These results indicate that HBx-induced deacetylation is important for proteasomal degradation of HIF-1a. Further, we observed that protein levels of MTA1 and HDAC1 were increased in the liver of HBxtransgenic mice. Also, there was a higher expression of HDAC1 in HCC than in the adjacent non-tumorous cirrhotic nodules in 10 out of 12 human HBV-associated HCC specimens. Together, our data indicate a positive cross talk between HBx and the MTA1/HDAC complex in stabilizing HIF-1a, which may play a critical role in angiogenesis and metastasis of HBV-associated HCC.

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Section: Discussionmentioning

confidence: 99%

Hepatitis B virus X protein induces the expression of MTA1 and HDAC1, which enhances hypoxia signaling in hepatocellular carcinoma cells

et al. 2008

Oncogene

142

129

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“…Recently, Arnesen et al [27] have reported evidence that the stability of HIF-1a is not regulated by hARD1 and that the level of hARD1 is not hypoxically regulated. These authors also reported evidence that hARD1 does not acetylate HIF1a, but importantly did demonstrate an interaction between hARD1 and HIF-1a.…”

Section: Note Added In Proofmentioning

confidence: 99%

Purified recombinant hARD1 does not catalyse acetylation of Lys₅₃₂ of HIF‐1α fragments in vitro

et al. 2006

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In humans, many responses to hypoxia including angiogenesis and erythropoiesis are mediated by the a/b-heterodimeric transcription factor hypoxia inducible factor (HIF). The stability and/or activity of human HIF-1a are modulated by post-translational modifications including prolyl and asparaginyl hydroxylation, phosphorylation, and reportedly by acetylation of the side-chain of Lys 532 by ARD1 (arrest defective protein 1 homologue), an acetyltransferase. Using purified recombinant human ARD1 (hARD1) we did not observe ARD1-mediated N-acetylation of Lys 532 using fragments of HIF-1a. However, recombinant hARD1 from Escherichia coli was produced with partial N-terminal acetylation and was observed to undergo slow self-mediated N-terminal acetylation. The observations are consistent with the other data indicating that hARD1, at least alone, does not acetylate HIF-1a, and with reports on the N-terminal acetyltransferase activity of a recently reported heterodimeric complex comprising hARD1 and N-acetyltransferase protein.

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“…In addition, ARD1 has been reported to show q-protein acetylation activity in mammalian cells; for example, it acetylates Lys 532 in hypoxia-inducible factor 1a (HIF-1a) and thereby degrades HIF-1a via the ubiquitin-proteasome system (7). However, two research groups recently posed questions about the involvement of ARD1 in HIF-1a regulation (8,9).…”

Section: Introductionmentioning

confidence: 99%

Human Arrest Defective 1 Acetylates and Activates β-Catenin, Promoting Lung Cancer Cell Proliferation

Lim¹,

Park²,

2006

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Arrest defective 1 (ARD1), an acetyltransferase, is essential for the yeast life cycle. Although its human homologue (hARD1) has been identified, its biological functions in human cells remain unclear. In the present study, we examined the biological function of hARD1. In H1299 and A549 lung cancer cells, hARD1-silencing RNA inhibited cell proliferation and induced G 1 arrest. Cyclin D1 was also found to be downregulated in these growth-arrested cells, and the ectopic expression of cyclin D1 rescued cell growth. hARD1 knockdown repressed the promoter activity of the cyclin D1 gene, which inhibited the transcription of cyclin D1. Moreover, hARD1 knockdown reduced the binding of B-catenin/TCF4 transcription factor to cyclin D1 promoter and repressed its transcriptional activity. Inversely, hARD1 expression increased the transcriptional activity of B-catenin. Both endogenous and ectopically expressed hARD1 was coimmunoprecipitated with B-catenin. hARD1 knockdown did not affect B-catenin expression or degradation but noticeably reduced acetylated B-catenin. The B-catenin binding and acetylation by hARD1 were observed in vitro. Therefore, it is suggested that hARD1 participates in proliferation of lung cancer cells via the activation of

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Interaction between HIF‐1α (ODD) and hARD1 does not induce acetylation and destabilization of HIF‐1α

Cited by 82 publications

References 26 publications

Hepatitis B virus X protein induces the expression of MTA1 and HDAC1, which enhances hypoxia signaling in hepatocellular carcinoma cells

Hepatitis B virus X protein induces the expression of MTA1 and HDAC1, which enhances hypoxia signaling in hepatocellular carcinoma cells

Purified recombinant hARD1 does not catalyse acetylation of Lys₅₃₂ of HIF‐1α fragments in vitro

Human Arrest Defective 1 Acetylates and Activates β-Catenin, Promoting Lung Cancer Cell Proliferation

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Interaction between HIF‐1α (ODD) and hARD1 does not induce acetylation and destabilization of HIF‐1α

Cited by 82 publications

References 26 publications

Hepatitis B virus X protein induces the expression of MTA1 and HDAC1, which enhances hypoxia signaling in hepatocellular carcinoma cells

Hepatitis B virus X protein induces the expression of MTA1 and HDAC1, which enhances hypoxia signaling in hepatocellular carcinoma cells

Purified recombinant hARD1 does not catalyse acetylation of Lys532 of HIF‐1α fragments in vitro

Human Arrest Defective 1 Acetylates and Activates β-Catenin, Promoting Lung Cancer Cell Proliferation

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Purified recombinant hARD1 does not catalyse acetylation of Lys₅₃₂ of HIF‐1α fragments in vitro