CoChat
Sign Up
Cited by 494TGF-β signaling in diseasesUbiquitin and proteasome pathwaysDevelopmental Biology and Gene Regulation

FAM/USP9x, a Deubiquitinating Enzyme Essential for TGFβ Signaling, Controls Smad4 Monoubiquitination

Open access
Dupont, Sirio, Mamidi, Anant, Cordenonsi, Michelangelo, Montagner, Marco, Zacchigna, Luca, Adorno, Maddalena, Martello, Graziano, Stinchfield, Michael J. +8 more·2009·Cell
DOI 10.1016/j.cell.2008.10.051
Open this paper in CoChat — free accountOpen PDF

Abstract

The assembly of the Smad complex is critical for TGFbeta signaling, yet the mechanisms that inactivate or empower nuclear Smad complexes are less understood. By means of siRNA screen we identified FAM (USP9x), a deubiquitinase acting as essential and evolutionarily conserved component in TGFbeta and bone morphogenetic protein signaling. Smad4 is monoubiquitinated in lysine 519 in vivo, a modification that inhibits Smad4 by impeding association with phospho-Smad2. FAM reverts this negative modification, re-empowering Smad4 function. FAM opposes the activity of Ectodermin/Tif1gamma (Ecto), a nuclear factor for which we now clarify a prominent role as Smad4 monoubiquitin ligase. Our study points to Smad4 monoubiquitination and deubiquitination as a way for cells to set their TGFbeta responsiveness: loss of FAM disables Smad4-dependent responses in several model systems, with Ecto being epistatic to FAM. This defines a regulative ubiquitination step controlling Smads that is parallel to those impinging on R-Smad phosphorylation.

Integrity signals

Registry

Crossref · 10.1016/j.cell.2008.10.051

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • GOF mut-p53 exhibits interactions with distinct transcription factors (e.g., NF-ɣ, SREBP, VDR, Sp1, ETS2, NFR2, p73, p63) that promote tumor initiation and progression.

    “In contrast to wt-p53, GOF mut-p53 exhibits interactions with distinct transcription factors (e.g., NF-ɣ, SREBP, VDR, Sp1, ETS2, NFR2, p73, p63) that promote tumor initiation and progression [13,72,73,74,75,76,77].”

    From The p53 Pathway in Glioblastoma (2018) · cites this paper as [75]

No citation lists for this paper

No citation lists for this paper yet — checked again daily.

References 35 · Cited by 494

Authors
Dupont, S., Mamidi, A., Cordenonsi, M., Montagner, M., Zacchigna, L., Adorno, M., Martello, G., Stinchfield, M. J., Soligo, S., Morsut, L., Inui, M., Moro, S., Modena, N., Argenton, F., Newfeld, S. J., & Piccolo, S.
Affiliations
  • University of Padua (IT)
  • Arizona State University (US)
Corresponding author
Piccolo, Stefano
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2009-01
Volume
136
Issue
1
Pages
123-135
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2008.10.051
OpenAlex
W2110272715
Cited by
494
References
35
Citations by year
2026: 9 · 2025: 20 · 2024: 18 · 2023: 14 · 2022: 25 · 2021: 22 · 2020: 34 · 2019: 32 · 2018: 25 · 2017: 24 · 2016: 32 · 2015: 36 · 2014: 34 · 2013: 30 · 2012: 56
FWCI
18.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, other-oa)
Funders
National Cancer Institute (R01CA095875, CA095875)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
deubiquitinase, SMAD4, monoubiquitination, TGF-beta signaling, ubiquitination, Smad2 phosphorylation, BMP signaling, epistasis
MeSH terms
Animals, Embryo, Nonmammalian, Transcription Factors, Xenopus, Signal Transduction, Transforming Growth Factor beta, Xenopus Proteins, Ubiquitin Thiolesterase, Cell Line, Tumor, Smad4 Protein, Ubiquitination

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review