Rac1 est la cible de l’activité E3 ubiquitine-ligase du suppresseur de tumeur HACE1

Gâcon, Gérard; Mettouchi, Amel; Lemichez, Emmanuel

doi:10.1051/medsci/2012281014

Cited by 3 publications

(2 citation statements)

References 12 publications

(19 reference statements)

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“…49 In fact, it has been recently described that Rac1 activity is regulated by the proteasomal machinery in other scenarios, and, as described in the introduction, the E3 ligases HACE1, c-IAP and XIAP are some examples. 13, 14, 15 Our MG-132 experiments clearly demonstrate that the activity of CED-10 during the engulfment is regulated by the proteasomal machinery as well. Concretely from the proteasomal machinery ligases, PDR-1 interacts with human Rac1and ubiquitylates CED-10.…”

Section: Discussionmentioning

confidence: 68%

“…Rac1 activity is regulated by the proteasomal machinery in other scenarios, and the E3 ligases HACE1, c-IAP and XIAP are some examples. 13, 14, 15 HACE-1 has been involved in the mechanism of pathogen infection and c-IAP and XIAP regulate carcinogenesis. 16, 17 In the IAPs context, the downregulation of the E3 ligases leads to an increase of Rac1 levels and activity in cells, promoting cell elongation and migration.…”

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confidence: 99%

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PDR-1/hParkin negatively regulates the phagocytosis of apoptotic cell corpses in Caenorhabditis elegans

Cabello

Sämann²,

Gómez-Orte

et al. 2014

Cell Death Dis

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Apoptotic cell death is an integral part of cell turnover in many tissues, and proper corpse clearance is vital to maintaining tissue homeostasis in all multicellular organisms. Even in tissues with high cellular turnover, apoptotic cells are rarely seen because of efficient clearance mechanisms in healthy individuals. In Caenorhabditis elegans, two parallel and partly redundant conserved pathways act in cell corpse engulfment. The pathway for cytoskeletal rearrangement requires the small GTPase CED-10 Rac1 acting for an efficient surround of the dead cell. The CED-10 Rac pathway is also required for the proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. Parkin, the mammalian homolog of the C. elegans PDR-1, interacts with Rac1 in aged human brain and it is also implicated with actin dynamics and cytoskeletal rearrangements in Parkinsons's disease, suggesting that it might act on engulfment. Our genetic and biochemical studies indicate that PDR-1 inhibits apoptotic cell engulfment and DTC migration by ubiquitylating CED-10 for degradation.

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Section: Discussionmentioning

confidence: 68%

mentioning

confidence: 99%

PDR-1/hParkin negatively regulates the phagocytosis of apoptotic cell corpses in Caenorhabditis elegans

Cabello

Sämann²,

Gómez-Orte

et al. 2014

Cell Death Dis

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Demethylation of the HACE1 gene promoter inhibits the proliferation of human liver cancer cells

Han

et al. 2019

Oncol Lett

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HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) is frequently downregulated or lost in numerous types of cancer, including liver cancer. The aim of the present study was to examine whether demethylation of the HACE1 gene could inhibit tumour progression. The expression of HACE1 was detected in liver cancer cell lines. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas)-based demethylation single guide RNAs for the HACE1 gene promoter were designed and transfected into liver cancer cells. Subsequently, proliferation was detected by MTT and colony formation assays, and optineurin (OPTN) ubiquitination and microtubule-associated proteins 1A/1B light chain 3B protein levels were detected by immunoblotting. The levels of HACE1 were significantly reduced in liver cancer cell lines compared with in a normal liver cell line. Demethylation of the HACE1 gene promoter increased HACE1 expression, inhibited the proliferation of liver cancer cells, and promoted OPTN ubiquitination and autophagy activity in liver cancer cells. In conclusion, activation of HACE1 expression by promoter demethylation may provide a suitable approach for anticancer therapy.

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Tumor-suppressive role of HACE1 in hepatocellular carcinoma and its clinical significance

Gao

Wu²,

Bai

et al. 2016

Oncology Reports

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An increasing body of evidence suggests that downregulation or deletion of HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) gene plays an important role in the occurrence, invasion and metastasis process in many human malignancies and is closely related to prognosis. However, sparse evidence exists concerning the precise function and clinical significance of HACE1 in hepatocellular carcinoma (HCC). In the present study, we investigated the expression pattern of HACE1 in HCC tissues and cell lines, and determined the potential functions of HACE1 in HCC cell lines and evaluated the relationships between HACE1 expression and clinicopathological characteristics. Protein and mRNA expression levels of HACE1 in human HCC tissues and cell lines were examined by western blot analysis, quantitative real‑time polymerase chain reaction and immunohistochemical (IHC) analyses. IHC was used to analyze the correlations between HACE1 expression and clinicopathological features. HACE1 was upregulated in SMCC7721 cells by transfection with pcDNA3.1-HACE1 and Huh7 cells were transfected with siRNA targeting HACE1 for downregulation. Cell Counting Κit-8, Transwell and wound healing assays were performed to investigate the effects of the overexpression and knockdown of HACE1 on cellular proliferation and migration. The results revealed that HACE1 expression was lower in the HCC tissues and cell lines at the mRNA and protein levels compared to levels noted in the matched non‑tumor tissues and the normal liver cell line L02. Knockdown of HACE1 in Huh7 cells accelerated cell proliferation and migration (P<0.05), and overexpression of HACE1 in SMCC7721 cells was found to decrease the capacity for proliferation and migration (P<0.01). The results of IHC suggested that the HACE1 expression level was closely related to the serum AFP level, tumor differentiation and vascular invasion (P<0.05). Patients with low HACE1 expression levels exhibited poorer overall survival and HACE1 was found to be an independent prognostic factor for survival. In conclusion, as a tumor suppressor, HACE1 may be a valuable prognostic biomarker and potential therapeutic target for HCC treatment.

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Rac1 est la cible de l’activité E3 ubiquitine-ligase du suppresseur de tumeur HACE1

Cited by 3 publications

References 12 publications

PDR-1/hParkin negatively regulates the phagocytosis of apoptotic cell corpses in Caenorhabditis elegans

PDR-1/hParkin negatively regulates the phagocytosis of apoptotic cell corpses in Caenorhabditis elegans

Demethylation of the HACE1 gene promoter inhibits the proliferation of human liver cancer cells

Tumor-suppressive role of HACE1 in hepatocellular carcinoma and its clinical significance

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