Characterisation of the human and mouse orthologues of the Drosophila &lt;i&gt;ariadne&lt;/i&gt; gene

Tan, Nancy G.S.; Ardley, Helen C.; Rose, Stephen A.; Leek, J.P.; Markham, Alexander F.; Robinson, Philip A.

doi:10.1159/000056780

Cited by 9 publications

(6 citation statements)

References 12 publications

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“…ARIH1 is a 557-amino-acid protein (64 kDa) distributed in the cytoplasm and the nuclei of cells ( Figure 1A; Elmehdawi et al, 2013) that shares many structural and functional properties with Parkin (Parelkar et al, 2012). It is highly conserved, sharing 72% and 98% amino acid sequence identity with the Drosophila and mouse genes, respectively (Tan et al, 2000). Despite the widespread distribution of ARIH1 transcripts (Moynihan et al, 1999) and the lethality of KOs (Aguilera et al, 2000), its cellular functions are not well characterized.…”

Section: Discussionmentioning

confidence: 99%

Parkin-Independent Mitophagy Controls Chemotherapeutic Response in Cancer Cells

et al. 2017

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Mitophagy is an evolutionarily conserved process that selectively targets impaired mitochondria for degradation. Defects in mitophagy are often associated with diverse pathologies, including cancer. Because the main known regulators of mitophagy are frequently inactivated in cancer cells, the mechanisms that regulate mitophagy in cancer cells are not fully understood. Here, we identified an E3 ubiquitin ligase (ARIH1/HHARI) that triggers mitophagy in cancer cells in a PINK1-dependent manner. We found that ARIH1/HHARI polyubiquitinates damaged mitochondria, leading to their removal via autophagy. Importantly, ARIH1 is widely expressed in cancer cells, notably in breast and lung adenocarcinomas; ARIH1 expression protects against chemotherapy-induced death. These data challenge the view that the main regulators of mitophagy are tumor suppressors, arguing instead that ARIH1-mediated mitophagy promotes therapeutic resistance.

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Section: Discussionmentioning

confidence: 99%

Parkin-Independent Mitophagy Controls Chemotherapeutic Response in Cancer Cells

et al. 2017

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“…One of the strongest hits in the screen was the parkin family ubiquitin ligase ariadne homologue 1 (ARIH1) (40). The ARIH1 SMARTpool and all four of the individual sequences tested in the deconvolution experiments significantly sensitized ES cells to CP-induced loss of viability ( Fig.…”

Section: A Ubiquitination Rnai Screen Identifies Cp Response Modulatorsmentioning

confidence: 99%

The E3 Ubiquitin Ligase ARIH1 Protects against Genotoxic Stress by Initiating a 4EHP-Mediated mRNA Translation Arrest

Stechow

Typas

Carreras-Puigvert

et al. 2015

Molecular and Cellular Biology

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bDNA damage response signaling is crucial for genome maintenance in all organisms and is corrupted in cancer. In an RNA interference (RNAi) screen for (de)ubiquitinases and sumoylases modulating the apoptotic response of embryonic stem (ES) cells to DNA damage, we identified the E3 ubiquitin ligase/ISGylase, ariadne homologue 1 (ARIH1). Silencing ARIH1 sensitized ES and cancer cells to genotoxic compounds and ionizing radiation, irrespective of their p53 or caspase-3 status. Expression of wild-type but not ubiquitinase-defective ARIH1 constructs prevented sensitization caused by ARIH1 knockdown. ARIH1 protein abundance increased after DNA damage through attenuation of proteasomal degradation that required ATM signaling. Accumulated ARIH1 associated with 4EHP, and in turn, this competitive inhibitor of the eukaryotic translation initiation factor 4E (eIF4E) underwent increased nondegradative ubiquitination upon DNA damage. Genotoxic stress led to an enrichment of ARIH1 in perinuclear, ribosome-containing regions and triggered 4EHP association with the mRNA 5= cap as well as mRNA translation arrest in an ARIH1-dependent manner. Finally, restoration of DNA damage-induced translation arrest in ARIH1-depleted cells by means of an eIF2 inhibitor was sufficient to reinstate resistance to genotoxic stress. These findings identify ARIH1 as a potent mediator of DNA damage-induced translation arrest that protects stem and cancer cells against genotoxic stress. DNA damage leads to acute toxicity and the accumulation of mutations and chromosomal instability, potentially resulting in malignant transformation (1, 2). To counteract these deleterious effects of DNA damage, the cell is equipped with a highly complex signaling response termed the DNA damage response (DDR). The DDR activates effector components involved in protective pathways, including DNA damage repair, cell cycle arrest, transcription regulation, chromatin remodeling, and cell death (1). The complex of DDR signaling pathways is crucial for the protection of the genome in all organisms. Moreover, understanding DDR signaling in the context of chemical or ionizing radiation-induced DNA damage is important to design improved strategies to combat therapy resistance. In tandem with phosphorylation-mediated signaling, which is largely executed by the phosphoinositol 3-kinase (PI3K)-like kinases ATM, ATR, and DNA-dependent protein kinase (DNA-PK), the checkpoint kinases Chk1 and Chk2, and members of the mitogen-activated protein kinase (MAPK) family (3, 4), protein modifications by ubiquitin and ubiquitin-like moieties are crucial at all levels of the DDR (5).The ubiquitination machinery can form various, differentially interpreted tags, including both degradative (K48-and K11-linked chains) and nondegradative (monoubiquitination and K63-linked chains) signals (6). Furthermore, a growing family of ubiquitin-like modifications, such as SUMO, Nedd8, and ISG15, has been identified, mostly providing nondegradative signals. Multiple enzymes are shared between the ubiquitinat...

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“…ARI14 is a member of the ARIADNE gene family that encodes putative E3 ubiquitin ligases (Tan et al 2000;Qiu and Fay 2006). Arabidopsis ARI8 was shown to exhibit E3 ubiquitin ligase activity (Stone et al 2005), thus it was presumed that other members of the ARIADNE-like family in Arabidopsis had similar activities.…”

Section: Kpl Plays a Key Role In Double Fertilizationmentioning

confidence: 99%

Proper regulation of a sperm-specific cis-nat-siRNA is essential for double fertilization in Arabidopsis

Ron¹,

Saez²,

Williams³

et al. 2010

Genes Dev.

160

182

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Natural cis-antisense siRNAs (cis-nat-siRNAs) are a recently characterized class of small regulatory RNAs that are widespread in eukaryotes. Despite their abundance, the importance of their regulatory activity is largely unknown. The only functional role for eukaryotic cis-nat-siRNAs that has been described to date is in environmental stress responses in plants. Here we demonstrate that cis-nat-siRNA-based regulation plays key roles in Arabidopsis reproductive function, as it facilitates gametophyte formation and double fertilization, a developmental process of enormous agricultural value. We show that male gametophytic kokopelli (kpl) mutants display frequent single-fertilization events, and that KPL and a inversely transcribed gene, ARIADNE14 (ARI14), which encodes a putative ubiquitin E3 ligase, generate a sperm-specific nat-siRNA pair. In the absence of KPL, ARI14 RNA levels in sperm are increased and fertilization is impaired. Furthermore, ARI14 transcripts accumulate in several siRNA biogenesis pathway mutants, and overexpression of ARI14 in sperm phenocopies the reduced seed set of the kokopelli mutants. These results extend the regulatory capacity of cis-nat-siRNAs to development by identifying a role for cis-nat-siRNAs in controlling sperm function during double fertilization. -nat-siRNAs (Okamura and Lai 2008;Werner et al. 2009). In plants, there are two studies demonstrating regulatory roles of cis-nat-siRNAs generated from two coding RNAs. In each case, one transcript of the cis-natsiRNA pair was constitutively expressed and the other was induced by stress, either abiotic (Borsani et al. 2005) or biotic (Katiyar-Agarwal et al. 2006). In both cases, down-regulation of the target gene by specific cis-natsiRNAs conferred tolerance to the inductive stress.In flowering plants, the male gametophyte (pollen grain) contains three cells: a vegetative cell that forms

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Characterisation of the human and mouse orthologues of the Drosophila <i>ariadne</i> gene

Cited by 9 publications

References 12 publications

Parkin-Independent Mitophagy Controls Chemotherapeutic Response in Cancer Cells

Parkin-Independent Mitophagy Controls Chemotherapeutic Response in Cancer Cells

The E3 Ubiquitin Ligase ARIH1 Protects against Genotoxic Stress by Initiating a 4EHP-Mediated mRNA Translation Arrest

Proper regulation of a sperm-specific cis-nat-siRNA is essential for double fertilization in Arabidopsis

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