ArticleThe Journal of biological chemistry2014
The CUL7/F-box and WD repeat domain containing 8 (CUL7/Fbxw8) ubiquitin ligase promotes degradation of hematopoietic progenitor kinase 1.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 46 citations in OpenAlex.
- CUL7-mediated KEAP1 ubiquitination promotes the progression of colon cancer via NRF2 signaling.Cell death & disease · 2026Article
- A Novel HomozygousClinical case reports · 2026Article
- The CRL7Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Do SalivaryCurrent issues in molecular biology · 2024Article
- Comprehensive analysis of the Cullin family of genes reveals that CUL7 and CUL9 are the significant prognostic biomarkers in colorectal cancer.American journal of translational research · 2024Article
- FBXW8 suppresses PDCoV proliferation via the NPD52-dependent autophagic degradation of a viral nucleocapsid protein.Frontiers in immunology · 2024Article
- Structure-based drug design of potential inhibitors of FBXW8, the substrate recognition component of Cullin-RING ligase 7.Molecular diversity · 2023Article
- Hematopoietic progenitor kinase 1 inhibits the development and progression of pancreatic intraepithelial neoplasia.The Journal of clinical investigation · 2023Article
- A Degradation Motif in STAU1 Defines a Novel Family of Proteins Involved in Inflammation.International journal of molecular sciences · 2022Article
- Identification and verification of the prognostic value of CUL7 in colon adenocarcinoma.Frontiers in immunology · 2022Article
- Pan-cancer analysis of FBXW family with potential implications in prognosis and immune infiltration.Frontiers in immunology · 2022Article
- The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer.Oncogenesis · 2020Review
- Review
- Functional roles of protein phosphatase 4 in multiple aspects of cellular physiology: a friend and a foe.BMB reports · 2020Review
- Hematopoietic progenitor kinase 1 down-regulates the oncogenic receptor tyrosine kinase AXL in pancreatic cancer.The Journal of biological chemistry · 2020Article
- F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.Theranostics · 2020Review
- Cullin-RING E3 Ubiquitin Ligase 7 in Growth Control and Cancer.Advances in experimental medicine and biology · 2020Review
- Prognostic values of F-box members in breast cancer: an online database analysis and literature review.Bioscience reports · 2019Review
- Prostate cancer cell proliferation is suppressed by microRNA-3160-5p via targeting of F-box and WD repeat domain containing 8.Oncology letters · 2018Article
- Chromatin-Bound Cullin-Ring Ligases: Regulatory Roles in DNA Replication and Potential Targeting for Cancer Therapy.Frontiers in molecular biosciences · 2018Review
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 5 institutions in 3 countries.
Funding
Abstract
HPK1, a member of mammalian Ste20-like serine/threonine kinases, is lost in >95% pancreatic cancer through proteasome-mediated degradation. However, the mechanism of HPK1 loss has not been defined. The aims of this study are to identify the ubiquitin ligase and to examine the mechanisms that targets HPK1 degradation. We found that the CUL7/Fbxw8 ubiquitin ligase targeted HPK1 for degradation via the 26 S proteasome. The ubiquitination of HPK1 required its kinase activity and autophosphorylation. Wild-type protein phosphatase 4 (PP4), but not the phosphatase-dead PP4 mutant, PP4-RL, inhibits the interaction of Fbxw8 with HPK1 and Fbxw8-mediated ubiquitination of HPK1. In addition, we showed that Thr-355 of HPK1 is a key PP4 dephosphorylation site, through which CUL7/Fbxw8 ubiquitin ligase and PP4 regulates HPK1 stability. Knockdown of Fbxw8 restores endogenous HPK1 protein expression and inhibits cell proliferation of pancreatic cancer cells. Our study demonstrated that targeted degradation of HPK1 by the CUL7/Fbxw8 ubiquitin ligase constitutes a negative-feedback loop to restrain the activity of HPK1 and that CUL7/Fbxw8 ubiquitin ligase promotes pancreatic cancer cell proliferation. CUL7/Fbxw8 ubiquitin ligase-mediated HPK1 degradation revealed a direct link and novel role of CUL7/Fbxw8 ubiquitin ligase in the MAPK pathway, which plays a critical role in cell proliferation and differentiation.
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.