Evidence map›Paper›PMID 29164996›Full record

ArticleAutophagy2018

CPTP: A sphingolipid transfer protein that regulates autophagy and inflammasome activation.

Shrawan Kumar Mishra, Yong-Guang Gao, Yibin Deng, Charles E Chalfant, Edward H Hinchcliffe, Rhoderick E Brown

Open access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% 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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

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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 2 institutions in 1 country.

Shrawan Kumar Mishraa Hormel Institute , University of Minnesota , Austin, MN USA.
Yong-Guang Gaoa Hormel Institute , University of Minnesota , Austin, MN USA.
Yibin Denga Hormel Institute , University of Minnesota , Austin, MN USA.
Charles E Chalfantb Department of Biochemistry & Molecular Biology, VCU Massey Cancer Center, VCU Institute of Molecular Medicine, VCU Johnson Center for Critical Care and Pulmonary Research , Virginia Commonwealth University , Richmond , VA USA.
Edward H Hinchcliffea Hormel Institute , University of Minnesota , Austin, MN USA.
Rhoderick E Browna Hormel Institute , University of Minnesota , Austin, MN USA.ORCID 0000-0002-7337-3604
University of Minnesota · USHunter Holmes McGuire VA Medical Center · US

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Kim Felder Rhoads · 1985 to 2026
$51.0M
The roles of ceramide and its derivatives in A. phagocytophilum pathogenesisR01AI139072 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI CHARLES E. CHALFANT, Jason A Carlyon · 2018 to 2026
$5.7M
GLYCOLIPID TRANSFER--REGULATION BY MEMBRANE INTERFACESR01GM045928 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BROWN, RHODERICK E · 1992 to 2014
$4.8M
The utilization of photonics technology to rapidly detect bioactive lipids associated with preeclampsia developmentU01HD087198 · NICHD · VIRGINIA COMMONWEALTH UNIVERSITY · PI CHALFANT, CHARLES E., WALSH, SCOTT W · 2015 to 2015
$4.2M
The functional role of the cPLA2alpha/C1P interaction in sepsis resolutionR01HL125353 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI BROWN, RHODERICK E, CHALFANT, CHARLES E. · 2014 to 2018
$4.0M
Mechanisms of Centrosome Reproduction in Animal CellsR01GM072754 · NIGMS · UNIVERSITY OF NOTRE DAME · PI HINCHCLIFFE, EDWARD H · 2005 to 2009
$1.3M
Gain of function mutant p53 in telomere uncapping-driven breast tumorigenesisR01CA160333 · NCI · UNIVERSITY OF MINNESOTA · PI DENG, YIBIN · 2011 to 2015
$1.2M
High Performance Cryogenic NMR ProbeS10RR015935 · NCRR · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI ZHOU, MING-MING · 2002 to 2002
$207k
BLRD Research Career Scientist Award ApplicationIK6BX004603 · VA · VA VETERANS ADMINISTRATION HOSPITAL · PI CHALFANT, CHARLES E. · 2019 to 2025
–
The role of RNA splicing in non-small cell lung cancerI01BX001792 · VA · VA VETERANS ADMINISTRATION HOSPITAL · PI CHALFANT, CHARLES E. · 2013 to 2024
–
BLRD VA I01 BX001792BLRD VA IK6 BX004603NCI NIH HHS P30 CA016059NCI NIH HHS R01 CA160333NCRR NIH HHS S10 RR015935NHLBI NIH HHS R01 HL125353NIAID NIH HHS R01 AI139072NICHD NIH HHS U01 HD087198NIGMS NIH HHS R01 GM045928NIGMS NIH HHS R01 GM072754
6 · The paper itself

Abstract

The macroautophagy/autophagy and inflammasome pathways are linked through their roles in innate immunity and chronic inflammatory disease. Ceramide-1-phosphate (C1P) is a bioactive sphingolipid that regulates pro-inflammatory eicosanoid production. Whether C1P also regulates autophagy and inflammasome assembly/activation is not known. Here we show that CPTP (a protein that traffics C1P from its site of phosphorylation in the trans-Golgi to target membranes) regulates both autophagy and inflammasome activation. In human epithelial cells, knockdown of CPTP (but not GLTP [glycolipid transfer protein]) or expression of C1P binding-site point mutants, stimulated an 8- to 10-fold increase in autophagosomes and altered endogenous LC3-II and SQSTM1/p62 protein expression levels. CPTP depletion-induced autophagy elevated early markers of autophagosome formation (Golgi-derived ATG9A-vesicles, WIPI1), required key phagophore assembly and elongation factors (ATG5, ATG7, ULK1), and suppressed MTOR phosphorylation and that of its downstream target, RPS6KB1/p70S6K. Wild-type CPTP overexpression exerted a protective effect against starvation-induced autophagy. In THP-1 macrophage-like surveillance cells, CPTP knockdown induced not only autophagy but also elevated CASP1/caspase-1 levels, and strongly increased IL1B/interleukin-1β and IL18 release via a NLRP3 (but not NLRC4) inflammasome-based mechanism, while only moderately increasing inflammatory (pyroptotic) cell death. Inflammasome assembly and activation stimulated by CPTP depletion were autophagy dependent. Elevation of intracellular C1P by exogenous C1P treatment (instead of CPTP inhibition) also induced autophagy and IL1B release. Our findings identify human CPTP as an endogenous regulator of early-stage autophagosome assembly and inflammasome-driven, pro-inflammatory cytokine generation and release.

Indexed as

AutophagyApoptosisAutophagy-Related ProteinsBinding SitesCarrier ProteinsCaspase 1CeramidesCytokinesDown-RegulationGolgi ApparatusHEK293 CellsHeLa CellsHumansInflammasomesInflammation MediatorsMembrane ProteinsATG9A protein, humanAutophagy-Related ProteinsCarrier ProteinsCaspase 1ceramide 1-phosphateCeramidesCytokinesInflammasomesInflammation Mediatorslipid transfer proteinMembrane ProteinsTOR Serine-Threonine KinasesVesicular Transport Proteinsautophagosome inductionautophagyceramide-1-phosphateceramide-1-phosphate transfer proteincytokine releaseinflammasome activationpyroptosissphingolipid rheostatsphingolipidssphingolipid transfer proteins

Identifiers

PMID29164996
PMCPMC6070007
OpenAlexW2768847879

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.