ArticleScientific reports2017
Identification of cancer-associated missense mutations in hace1 that impair cell growth control and Rac1 ubiquitylation.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Review
- Identification of a putative founder effect involving the HACE1:c.1396C>T variant in two Iranian families and review of reported cases.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- HACE1 as a bridge between oxidative stress and autophagy.Frontiers in immunology · 2025Review
- Structural mechanisms of autoinhibition and substrate recognition by the ubiquitin ligase HACE1.Nature structural & molecular biology · 2024Article
- Inhibition of esophageal cancer progression through HACE1-TRIP12 interaction and associated RAC1 ubiquitination and degradation.Journal of Cancer · 2024Article
- Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Ubiquitylation of cyclin C by HACE1 regulates cisplatin-associated sensitivity in gastric cancer.Clinical and translational medicine · 2022Article
- Article
- Review
- Structural Insights into Ankyrin Repeat-Containing Proteins and Their Influence in Ubiquitylation.International journal of molecular sciences · 2021Review
- The interplay of Rac1 activity, ubiquitination and GDI binding and its consequences for endothelial cell spreading.PloS one · 2021Article
- HACE1 Prevents Lung Carcinogenesis via Inhibition of RAC-Family GTPases.Cancer research · 2020Article
- Review
- Ubiquitination and Long Non-coding RNAs Regulate Actin Cytoskeleton Regulators in Cancer Progression.International journal of molecular sciences · 2019Review
- The role of Rac in tumor susceptibility and disease progression: from biochemistry to the clinic.Biochemical Society transactions · 2018Review
- CNF1-like deamidase domains: common Lego bricks among cancer-promoting immunomodulatory bacterial virulence factors.Pathogens and disease · 2018Review
- Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration.Cancer medicine · 2018Article
- The pro-tumoral function of HACE1.Oncoscience · 2018Article
- Group-I PAKs-mediated phosphorylation of HACE1 at serine 385 regulates its oligomerization state and Rac1 ubiquitination.Scientific reports · 2018Article
- The Rac GTPase in Cancer: From Old Concepts to New Paradigms.Cancer research · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The E3 ubiquitin ligase HACE1 is a potent tumor suppressor that controls cell proliferation and ubiquitylates the small GTPase Rac1 to target it to proteasomal degradation. Whether and how the activity of HACE1 is regulated by the N-terminal ankyrin (ANK) and the middle (MID) domains is ill defined. Here, we identified in the version 64 of the Catalogue of Somatic Mutations in Cancer (COSMIC) 13 missense mutations of hace1 located outside the HECT domain, and found that all lead to defective control of cell proliferation. In addition, several mutations located in the ankyrin domain displayed a dramatic reduction in Rac1 ubiquitylation associated with a decrease of colony formation in soft agar. 3D structure modelling of the 7 ankyrin-repeats coupled to functional analysis identified a surface epitope centered on one of the mutated residue, Gly-175, which is critical for controlling Rac1 binding and ubiquitylation. We also identified a role for the MID domain in conferring the specificity of association of HACE1 to the active form of Rac1. Our study of the functional interplay between HACE1 and Rac1 in cancer thus sheds a new light on the molecular mechanism of Rac1 ubiquitylation by HACE1 and the impact of its cancer-associated mutations in cell proliferation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.