Evidence map›Paper›PMID 25431135›Full record

ArticleJournal of cell science2015

Nuclear FAM21 participates in NF-κB-dependent gene regulation in pancreatic cancer cells.

Zhi-Hui Deng, Timothy S Gomez, Douglas G Osborne, Christine A Phillips-Krawczak, Jin-San Zhang, Daniel D Billadeau

Open access · greenAbstract read
In one paragraph

Article in Journal of cell science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
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  5. Nuclear VPS35 attenuates NHEJ repair by sequestering Ku protein.Molecular medicine (Cambridge, Mass.) · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Zhi-Hui DengDivision of Oncology Research and Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA Department of Pathophysiology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, China.
Timothy S GomezDivision of Oncology Research and Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Douglas G OsborneDivision of Oncology Research and Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Christine A Phillips-KrawczakDivision of Oncology Research and Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Jin-San ZhangDivision of Oncology Research and Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA Key Laboratory of Biotechnology and Pharmaceutical Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China zhang.jinsan@mayo.edu billadeau.daniel@mayo.edu.
Daniel D BilladeauDivision of Oncology Research and Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA Department of Immunology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA zhang.jinsan@mayo.edu billadeau.daniel@mayo.edu.
Mayo Clinic · USNovel (United States) · USWenzhou Medical University · CN

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
Tissue CoreP50CA102701 · NCI · MAYO CLINIC ROCHESTER · PI PETERSEN, GLORIA M. · 2004 to 2018
$32.7M
Regulation of Actin Dynamics During T Cell ActivationR01AI065474 · NIAID · MAYO CLINIC ROCHESTER · PI BILLADEAU, DANIEL D · 2005 to 2014
$3.1M
TRAINING PROGRAM IN ALLERGIC DISEASEST32AI007047 · NIAID · MAYO CLINIC ROCHESTER · PI KITA, HIROHITO · 1985 to 2016
$2.0M
Tumor Microenvironment/Angiogenesis Training GrantT32CA148073 · NCI · MAYO CLINIC ROCHESTER · PI MC NIVEN, MARK A. · 2010 to 2014
$1.2M
NCI NIH HHS P30 CA015083NCI NIH HHS P30CA15083NCI NIH HHS P50 CA102701NCI NIH HHS P50CA102701NCI NIH HHS T32 CA148073NCI NIH HHS T32CA148073NIAID NIH HHS R01 AI065474NIAID NIH HHS R01AI065474NIAID NIH HHS T32 AI007047NIAID NIH HHS T32AI07047
6 · The paper itself

Abstract

The pentameric WASH complex is best known for its role in regulating receptor trafficking from retromer-rich endosomal subdomains. FAM21 functions to stabilize the WASH complex through its N-terminal head domain and localizes it to endosomes by directly binding the retromer through its extended C-terminal tail. Herein, we used affinity purification combined with mass spectrometry to identify additional FAM21-interacting proteins. Surprisingly, multiple components of the nuclear factor κB (NF-κB) pathway were identified, including the p50 and p65 (RelA) NF-κB subunits. We show that FAM21 interacts with these components and regulates NF-κB-dependent gene transcription at the level of p65 chromatin binding. We further demonstrate that FAM21 contains a functional monopartite nuclear localization signal sequence (NLS) as well as a CRM1/exportin1-dependent nuclear export signal (NES), both of which work jointly with the N-terminal head domain and C-terminal retromer recruitment domain to regulate FAM21 cytosolic and nuclear subcellular localization. Finally, our findings indicate that FAM21 depletion sensitizes pancreatic cancer cells to gemcitabine and 5-fluorouracil. Thus, FAM21 not only functions as an integral component of the cytoplasmic WASH complex, but also modulates NF-κB gene transcription in the nucleus.

Indexed as

Cell Line, TumorCell NucleusChromatinCytoplasmDeoxycytidineDrug Resistance, NeoplasmGemcitabineHumansMicrofilament ProteinsNF-kappa BNuclear Localization SignalsPancreatic NeoplasmsPhosphate-Binding ProteinsProtein BindingProteinsTranscription Factor RelAChromatinDeoxycytidineGemcitabineMicrofilament ProteinsNF-kappa BNuclear Localization SignalsPhosphate-Binding ProteinsProteinsRELA protein, humanTranscription Factor RelAWASHC2C protein, humanWASH protein, humanFAM21NF-κBPancreatic cancerRetromerWASH complex

Identifiers

PMID25431135
PMCPMC4294779
OpenAlexW2316238346

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.