ArticleCellular and molecular life sciences : CMLS2012
Palmitoylation by DHHC3 is critical for the function, expression, and stability of integrin α6β4.
Article in Cellular and molecular life sciences : CMLS, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 53 citations in OpenAlex.
- DHHC3-dependent S-Acylation of CRY1 regulates its subcellular localization and repressor function in the circadian clock.bioRxiv : the preprint server for biology · 2026Article
- Palmitoylation: an emerging therapeutic target bridging physiology and disease.Cellular & molecular biology letters · 2025Review
- zDHHC-Mediated S-Palmitoylation in Skin Health and Its Targeting as a Treatment Perspective.International journal of molecular sciences · 2025Review
- The CP123L protein of African swine fever virus is a membrane-associated, palmitoylated protein required for viral replication.Journal of virology · 2025Article
- The role of protein S-acylation in vascular injury associated with metabolic disorders.Frontiers in endocrinology · 2025Review
- S-palmitoylation: a novel insight in the development and immunotherapy of oral squamous cell carcinoma.Journal of Cancer · 2025Review
- S-acylation of CaChronic diseases and translational medicine · 2024Review
- Mechanisms and functions of protein S-acylation.Nature reviews. Molecular cell biology · 2024Review
- zDHHC3-mediated S-palmitoylation of SLC9A2 regulates apoptosis in kidney clear cell carcinoma.Journal of cancer research and clinical oncology · 2024Article
- QSOX2 Upregulated in triple-negative breast cancer exacerbates patient prognosis by stabilizing integrin β1.Heliyon · 2024Article
- Protein S-palmitoylation modification: implications in tumor and tumor immune microenvironment.Frontiers in immunology · 2024Review
- Protein palmitoylation in cancer: molecular functions and therapeutic potential.Molecular oncology · 2023Review
- Structural Exploration on Palmitoyltransferase DHHC3 fromPolymers · 2022Article
- Antioxidant and Anticancer Functions of Protein Acyltransferase DHHC3.Antioxidants (Basel, Switzerland) · 2022Review
- Multiscale modelling of claudin-based assemblies: A magnifying glass for novel structures of biological interfaces.Computational and structural biotechnology journal · 2022Review
- Protein cysteine palmitoylation in immunity and inflammation.The FEBS journal · 2021Review
- EGFR-dependent tyrosine phosphorylation of integrin β4 is not required for downstream signaling events in cancer cell lines.Scientific reports · 2021Article
- Antioxidant functions of DHHC3 suppress anti-cancer drug activities.Cellular and molecular life sciences : CMLS · 2021Article
- Understanding the role of integrins in breast cancer invasion, metastasis, angiogenesis, and drug resistance.Oncogene · 2021Review
- Putative Role of Protein Palmitoylation in Cardiac Lipid-Induced Insulin Resistance.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The laminin-binding integrin α6β4 plays key roles in both normal epithelial and endothelial cells and during tumor cell progression, metastasis, and angiogenesis. Previous cysteine mutagenesis studies have suggested that palmitoylation of α6β4 protein supports a few integrin-dependent functions and molecular associations. Here we took another approach and obtained strikingly different results. We used overexpression and RNAi knockdown in multiple cell types to identify protein acyl transferase DHHC3 as the enzyme responsible for integrin β4 and α6 palmitoylation. Ablation of DHHC3 markedly diminished integrin-dependent cellular cable formation on Matrigel, integrin signaling through Src, and β4 phosphorylation on key diagnostic amino acids (S1356 and 1424). However, unexpectedly, and in sharp contrast to prior α6β4 mutagenesis results, knockdown of DHHC3 accelerated the degradation of α6β4, likely due to an increase in endosomal exposure to cathepsin D. When proteolytic degradation was inhibited (by Pepstatin A), rescued α6β4 accumulated intracellularly, but was unable to reach the cell surface. DHHC3 ablation effects were strongly selective for α6β4. Cell-surface levels of ~10 other proteins (including α3β1) were not diminished, and the appearance of hundreds of other palmitoylated proteins was not altered. Results obtained here demonstrate a new substrate for the DHHC3 enzyme and provide novel opportunities for modulating α6β4 expression, distribution, and function.
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.