Evidence map›Paper›PMID 22770219›Full record

ArticleCell2012

Acetylation-dependent regulation of Skp2 function.

Hiroyuki Inuzuka, Daming Gao, Lydia W S Finley, Wen Yang, Lixin Wan, Hidefumi Fukushima, Y Rebecca Chin, Bo Zhai, Shavali Shaik, Alan W Lau and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed
8.2field-weighted citation impact, top 2% 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

146 citing papers in PubMed, 237 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. E3 ubiquitin ligase SKP2 limits autophagosome formation duringFrontiers in cellular and infection microbiology · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
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  20. Chromosomal copy number amplification-driven Linc01711 contributes to gastric cancer progression through histone modification-mediated reprogramming of cholesterol metabolism.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024
    Article

86 more citing papers are in PubMed but not listed here.

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

18 authors at 4 institutions in 2 countries.

Hiroyuki InuzukaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Daming Gao
Lydia W S Finley
Wen Yang
Lixin Wan
Hidefumi Fukushima
Y Rebecca Chin
Bo Zhai
Shavali Shaik
Alan W Lau
Zhiwei Wang
Steven P Gygi
Keiko Nakayama
Julie Teruya-Feldstein
Alex Toker
Marcia C Haigis
Pier Paolo Pandolfi
Wenyi Wei
Harvard University · USBeth Israel Deaconess Medical Center · USMemorial Sloan Kettering Cancer Center · USTohoku University · JP

Funding

Interplay between Cdh1 and major regulatory pathways in human cancerR01GM089763 · NIGMS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WEI, WENYI · 2009 to 2018
$3.0M
The Akt and NFAT Pathway and the Regulaton of Cancer Cell MotilityR01CA122099 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI TOKER, ALEX · 2007 to 2011
$1.4M
Functional analysis of beta-TRCP in cell cycle control and DNA damage responseR01GM094777 · NIGMS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WEI, WENYI · 2012 to 2015
$1.3M
New insights into the role of the Fbw7 tumor suppressor in senescence and agingK01AG041218 · NIA · BETH ISRAEL DEACONESS MEDICAL CENTER · PI INUZUKA, HIROYUKI · 2011 to 2015
$621k
NCI NIH HHS CA122099NCI NIH HHS R01 CA122099NIA NIH HHS AG041218NIA NIH HHS K01 AG041218NIGMS NIH HHS GM089763NIGMS NIH HHS GM094777NIGMS NIH HHS R01 GM089763NIGMS NIH HHS R01 GM094777
6 · The paper itself

Abstract

Aberrant Skp2 signaling has been implicated as a driving event in tumorigenesis. Although the underlying molecular mechanisms remain elusive, cytoplasmic Skp2 correlates with more aggressive forms of breast and prostate cancers. Here, we report that Skp2 is acetylated by p300 at K68 and K71, which is a process that can be antagonized by the SIRT3 deacetylase. Inactivation of SIRT3 leads to elevated Skp2 acetylation, which leads to increased Skp2 stability through impairment of the Cdh1-mediated proteolysis pathway. As a result, Skp2 oncogenic function is increased, whereby cells expressing an acetylation-mimetic mutant display enhanced cellular proliferation and tumorigenesis in vivo. Moreover, acetylation of Skp2 in the nuclear localization signal (NLS) promotes its cytoplasmic retention, and cytoplasmic Skp2 enhances cellular migration through ubiquitination and destruction of E-cadherin. Thus, our study identifies an acetylation-dependent regulatory mechanism governing Skp2 oncogenic function and provides insight into how cytoplasmic Skp2 controls cellular migration.

Indexed as

Cell MovementAcetylationAmino Acid SequenceAnimalsBreast NeoplasmsCadherinsCasein Kinase ICell Line, TumorCytoplasmDisease Models, AnimalHumansLysineMaleMiceMolecular Sequence Datap300-CBP-Associated FactorCadherinsCasein Kinase ILysinep300-CBP-Associated Factorp300-CBP Transcription FactorsProtein Sorting SignalsS-Phase Kinase-Associated Proteins

Identifiers

PMID22770219
PMCPMC3595190
OpenAlexW2011540184

What OpenQuestion holds

Textmetadata
LicenceTDM
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.