XIAP upregulates expression of HIF target genes by targeting HIF1α for Lys63-linked polyubiquitination

Park, Catherine V.; Ivanova, Iglika G.; Kenneth, Niall S.

doi:10.1093/nar/gkx549

Cited by 26 publications

(33 citation statements)

References 39 publications

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“…K63-linked polyubiquitination of HIF-1α catalyzed by TRAF6 can protect it from degradation [146]. XIAP modifies HIF-1α by K63-linked polyubiquitination to promote its nuclear retention and enhance HIF-dependent gene expression [147]. In conclusion, ubiquitination is an important regulatory mechanism of HIF-1.…”

Section: Ubiquitination and Transcription Factorsmentioning

confidence: 93%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

277

178

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Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

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Section: Ubiquitination and Transcription Factorsmentioning

confidence: 93%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

277

178

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“…Cells were lysed in 8 M urea lysis buffer and immunoblotted as described ( 21 ). Antibodies used were HIF1α (Clone 241809, R&D systems), HIF2α (#7096, Cell Signaling Technologies), phospho- eIF2α (Ser 51) (#9721, Cell Signaling Technologies), eIF2α (#5324, Cell Signaling Technologies), PERK (#3192, Cell Signaling Technologies), YB-1 (A303–231A, Bethyl), β-tubulin (#2146, Cell Signaling Technologies), VHL (#68547, Cell Signaling Technologies), β-actin (AC-74, Sigma).…”

Section: Methodsmentioning

confidence: 99%

PERK/eIF2α signaling inhibits HIF-induced gene expression during the unfolded protein response via YB1-dependent regulation of HIF1α translation

Ivanova

Park

Yemm

et al. 2018

Nucleic Acids Research

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HIF1α (hypoxia inducible factor 1α) is the central regulator of the cellular response to low oxygen and its activity is deregulated in multiple human pathologies. Consequently, given the importance of HIF signaling in disease, there is considerable interest in developing strategies to modulate HIF1α activity and down-stream signaling events. In the present study we find that under hypoxic conditions, activation of the PERK branch of the unfolded protein response (UPR) can suppress the levels and activity of HIF1α by preventing efficient HIF1α translation. Activation of PERK inhibits de novo HIF1α protein synthesis by preventing the RNA-binding protein, YB-1, from interacting with the HIF1α mRNA 5′UTR. Our data indicate that activation of the UPR can sensitise tumor cells to hypoxic stress, indicating that chemical activation of the UPR could be a strategy to target hypoxic malignant cancer cells.

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“…It was found that apoptotic nuclei could be seen in the muscle tissue of dermatomyositis, and the expression of apoptotic factors was upregulated, suggesting that apoptotic cells might be involved in the pathological process of dermatomyositis. [ 42 ] XAF1-related excessive apoptosis may exist in dermatomyositis, which may be one of the causes of dermatomyositis. [ 43 ]…”

Section: Discussionmentioning

confidence: 99%

Study on the differentially expressed genes and signaling pathways in dermatomyositis using integrated bioinformatics method

Liu

Zhao

2020

Medicine

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Dermatomyositis is a common connective tissue disease. The occurrence and development of dermatomyositis is a result of multiple factors, but its exact pathogenesis has not been fully elucidated. Here, we used biological information method to explore and predict the major disease related genes of dermatomyositis and to find the underlying pathogenic molecular mechanism. The gene expression data of GDS1956, GDS2153, GDS2855, and GDS3417 including 94 specimens, 66 cases of dermatomyositis specimens and 28 cases of normal specimens, were obtained from the Gene Expression Omnibus database. The 4 microarray gene data groups were combined to get differentially expressed genes (DEGs). The gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were operated by the database for annotation, visualization and integrated discovery and KEGG orthology based annotation system databases, separately. The protein–protein interaction networks of the DEGs were built from the STRING website. A total of 4097 DEGs were extracted from the 4 Gene Expression Omnibus datasets, of which 2213 genes were upregulated, and 1884 genes were downregulated. Gene ontology analysis indicated that the biological functions of DEGs focused primarily on response to virus, type I interferon signaling pathway and negative regulation of viral genome replication. The main cellular components include extracellular space, cytoplasm, and blood microparticle. The molecular functions include protein binding, double-stranded RNA binding and MHC class I protein binding. KEGG pathway analysis showed that these DEGs were mainly involved in the toll-like receptor signaling pathway, cytosolic DNA-sensing pathway, RIG-I-like receptor signaling pathway, complement and coagulation cascades, arginine and proline metabolism, phagosome signaling pathway. The following 13 closely related genes, XAF1, NT5E, UGCG, GBP2, TLR3, DDX58, STAT1, GBP1, PLSCR1, OAS3, SP100, IGK, and RSAD2, were key nodes from the protein–protein interaction network. This research suggests that exploring for DEGs and pathways in dermatomyositis using integrated bioinformatics methods could help us realize the molecular mechanism underlying the development of dermatomyositis, be of actual implication for the early detection and prophylaxis of dermatomyositis and afford reliable goals for the curing of dermatomyositis.

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XIAP upregulates expression of HIF target genes by targeting HIF1α for Lys63-linked polyubiquitination

Cited by 26 publications

References 39 publications

The role of ubiquitination and deubiquitination in cancer metabolism

The role of ubiquitination and deubiquitination in cancer metabolism

PERK/eIF2α signaling inhibits HIF-induced gene expression during the unfolded protein response via YB1-dependent regulation of HIF1α translation

Study on the differentially expressed genes and signaling pathways in dermatomyositis using integrated bioinformatics method

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