ArticleOncogene2008
Smad7 is inactivated through a direct physical interaction with the LIM protein Hic-5/ARA55.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 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
35 citing papers in PubMed, 55 citations in OpenAlex.
- Scaffold Proteins in Fibrotic Diseases of Visceral Organs.Biomolecules · 2025Review
- Physiological and pathological roles of Hic‑5 in several organs (Review).International journal of molecular medicine · 2022Review
- Therapeutic Mechanism and Clinical Observation of Traditional Chinese Medicine Combined with Interventional Recanalization for Tubal Infertility.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Paxillin family of focal adhesion adaptor proteins and regulation of cancer cell invasion.International review of cell and molecular biology · 2020Article
- The focal adhesion scaffold protein Hic-5 regulates vimentin organization in fibroblasts.Molecular biology of the cell · 2019Article
- HIC-5 in cancer-associated fibroblasts contributes to esophageal squamous cell carcinoma progression.Cell death & disease · 2019Article
- Alleviation of murine osteoarthritis by deletion of the focal adhesion mechanosensitive adapter, Hic-5.Scientific reports · 2019Article
- Hydrogen peroxide inducible clone-5 sustains NADPH oxidase-dependent reactive oxygen species-c-jun N-terminal kinase signaling in hepatocellular carcinoma.Oncogenesis · 2019Article
- TGF-BETA IN THE NATURAL HISTORY OF PROSTATE CANCER.Acta clinica Croatica · 2019Review
- Label-Free LC-MS/MS Proteomics Analyses Reveal Proteomic Changes AccompanyingBioMed research international · 2019Article
- Article
- Hic-5 regulates epithelial to mesenchymal transition in ovarian cancer cells in a TGFβ1-independent manner.Oncotarget · 2017Article
- Oncostatin M promotes cancer cell plasticity through cooperative STAT3-SMAD3 signaling.Oncogene · 2017Article
- Glucocorticoid receptor binding to chromatin is selectively controlled by the coregulator Hic-5 and chromatin remodeling enzymes.The Journal of biological chemistry · 2017Article
- Article
- Regulation of TGF-β Family Signaling by Inhibitory Smads.Cold Spring Harbor perspectives in biology · 2017Review
- Signal Transduction Pathways of EMT Induced by TGF-β, SHH, and WNT and Their Crosstalks.Journal of clinical medicine · 2016Review
- Hic-5 is required for myofibroblast differentiation by regulating mechanically dependent MRTF-A nuclear accumulation.Journal of cell science · 2016Article
- CDKN2B Regulates TGFβ Signaling and Smooth Muscle Cell Investment of Hypoxic Neovessels.Circulation research · 2016Article
- Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression.Oncotarget · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We recently reported that hydrogen peroxide-inducible clone-5 (Hic-5, also named androgen receptor-associated protein 55) can bind to the transforming growth factor-beta (TGF-beta)-signaling regulator Smad3, thereby inhibiting certain Smad3-dependent TGF-beta responses. We now show that Hic-5 can also control TGF-beta responses through an alternative mechanism involving Smad7, a key negative regulator of TGF-beta signaling. Hic-5 binds directly to Smad7. This interaction requires the LIM3 domain of Hic-5, and enhances TGF-beta signaling through causing loss of Smad7 protein but not mRNA. Enforced expression of Hic-5 reverses the ability of Smad7 to suppress TGF-beta-induced phosphorylation of Smads 2 and 3 and activation of the plasminogen activator inhibitor-1 promoter (in NRP-154 and PC3 prostate carcinoma and WPMY-1 prostate myofibroblast cell lines). Lentiviral-mediated small-hairpin RNA silencing of endogenous Hic-5 reduced TGF-beta responses in PC3 and WPMY-1 cells. Further work suggests that the level of Smad7 is modulated by its physical interaction with Hic-5 and targeted to a degradation pathway not likely to be proteasomal. Our findings support that Hic-5 functions as a cell-type-specific activator of TGF-beta signaling through its ability to physically interact with and neutralize Smad7.
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.