Evidence map›Paper›PMID 26314710›Full record

ArticleGenes & development2015

Proteomic analysis of pRb loss highlights a signature of decreased mitochondrial oxidative phosphorylation.

Brandon N Nicolay, Paul S Danielian, Filippos Kottakis, John D Lapek, Ioannis Sanidas, Wayne O Miles, Mantre Dehnad, Katrin Tschöp, Jessica J Gierut, Amity L Manning and 6 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
–field-weighted citation impact
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

61 citing papers in PubMed, 87 citations in OpenAlex.

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  10. Dual roles of β-arrestin 1 in mediating cell metabolism and proliferation in gastric cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022
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1 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

16 authors at 3 institutions in 2 countries.

Brandon N NicolayMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
Paul S DanielianDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
Filippos KottakisMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
John D LapekMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
Ioannis SanidasMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
Wayne O MilesMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
Mantre DehnadMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA; University Medical Center Utrecht, Utrecht 3584CX, Netherlands.
Katrin TschöpMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
Jessica J GierutMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
Amity L ManningMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
Robert MorrisMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
Kevin HaigisMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
Nabeel BardeesyMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
Jacqueline A LeesDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
Wilhelm HaasMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
Nicholas J DysonMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
Harvard University · USMassachusetts General Hospital · USMassachusetts Institute of Technology · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
USE OF RETROVIRUS PROMOTER TRAP VECTORS TO IDENTIFY ONCOGENES AND ANTI-ONCOGENESP01CA042063 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEES, JACQUELINE A. · 1986 to 2021
$30.5M
Dissection and manipulation of RB functionR01CA163698 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DYSON, NICHOLAS J · 2012 to 2016
$1.8M
Manipulating chromosome structure to suppress genome instabilityR00CA182731 · NCI · WORCESTER POLYTECHNIC INSTITUTE · PI MANNING, AMITY · 2015 to 2017
$747k
Understanding the role of SKP2 in small cell lung cancer progressionF32CA165856 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI NICOLAY, BRANDON · 2012 to 2014
$149k
NCI NIH HHS 2-P01-CA42063NCI NIH HHS F32 CA165856NCI NIH HHS F32-CA165856NCI NIH HHS P01 CA042063NCI NIH HHS P30 CA014051NCI NIH HHS P30-CA14051NCI NIH HHS R00 CA182731NCI NIH HHS R01 CA163698NCI NIH HHS R01-CA163698
6 · The paper itself

Abstract

The retinoblastoma tumor suppressor (pRb) protein associates with chromatin and regulates gene expression. Numerous studies have identified Rb-dependent RNA signatures, but the proteomic effects of Rb loss are largely unexplored. We acutely ablated Rb in adult mice and conducted a quantitative analysis of RNA and proteomic changes in the colon and lungs, where Rb(KO) was sufficient or insufficient to induce ectopic proliferation, respectively. As expected, Rb(KO) caused similar increases in classic pRb/E2F-regulated transcripts in both tissues, but, unexpectedly, their protein products increased only in the colon, consistent with its increased proliferative index. Thus, these protein changes induced by Rb loss are coupled with proliferation but uncoupled from transcription. The proteomic changes in common between Rb(KO) tissues showed a striking decrease in proteins with mitochondrial functions. Accordingly, RB1 inactivation in human cells decreased both mitochondrial mass and oxidative phosphorylation (OXPHOS) function. RB(KO) cells showed decreased mitochondrial respiratory capacity and the accumulation of hypopolarized mitochondria. Additionally, RB/Rb loss altered mitochondrial pyruvate oxidation from (13)C-glucose through the TCA cycle in mouse tissues and cultured cells. Consequently, RB(KO) cells have an enhanced sensitivity to mitochondrial stress conditions. In summary, proteomic analyses provide a new perspective on Rb/RB1 mutation, highlighting the importance of pRb for mitochondrial function and suggesting vulnerabilities for treatment.

Indexed as

Oxidative PhosphorylationAnimalsCells, CulturedColonGene Expression RegulationGene Knockout TechniquesHumansLungMiceMitochondriaMitochondrial ProteinsProteomicsRetinoblastoma ProteinStress, PhysiologicalTranscriptomeMitochondrial ProteinsRetinoblastoma Protein13C-glucosemetabolismmitochondriaOXPHOSpRBproteomics

Identifiers

PMID26314710
PMCPMC4573859
OpenAlexW2149852478

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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.