Evidence map›Paper›PMID 26044153›Full record

ArticleScientific reports2015

Membrane proximal ectodomain cleavage of MUC16 occurs in the acidifying Golgi/post-Golgi compartments.

Srustidhar Das, Prabin D Majhi, Mona H Al-Mugotir, Satyanarayana Rachagani, Paul Sorgen, Surinder K Batra

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

37 citing papers in PubMed, 55 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 1 institution in 1 country.

Srustidhar DasDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Prabin D MajhiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Mona H Al-MugotirDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Satyanarayana RachaganiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Paul SorgenDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Surinder K Batra1] Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA [2] Department of Pathology, University of Nebraska Medical Center, Omaha, NE 68198, USA [3] Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
University of Nebraska Medical Center · US

Funding

Tissue CoreP50CA127297 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI HOLLINGSWORTH, MICHAEL A. · 2008 to 2018
$17.1M
Early Diagnosis of Pancreatic CancerU01CA111294 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., HOLLINGSWORTH, MICHAEL A. · 2004 to 2015
$7.1M
Role of N-Cadherin in Pancreatic Tumor MicroenvironmentU54CA163120 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K. · 2011 to 2015
$4.2M
NCI NIH HHS P50 CA127297NCI NIH HHS U01 CA111294NCI NIH HHS U54 CA163120
6 · The paper itself

Abstract

MUC16, precursor of the most widely used ovarian cancer biomarker CA125, is up regulated in multiple malignancies and is associated with poor prognosis. While the pro-tumorigenic and metastatic roles of MUC16 are ascribed to the cell-associated carboxyl-terminal MUC16 (MUC16-Cter), the exact biochemical nature of MUC16 cleavage generating MUC16-Cter has remained unknown. Using different lengths of dual-epitope (N-terminal FLAG- and C-terminal HA-Tag) tagged C-terminal MUC16 fragments, we demonstrate that MUC16 cleavage takes place in the juxta-membrane ectodomain stretch of twelve amino acids that generates a ~17 kDa cleaved product and is distinct from the predicted sites. This was further corroborated by domain swapping experiment. Further, the cleavage of MUC16 was found to take place in the Golgi/post-Golgi compartments and is dependent on the acidic pH in the secretory pathway. A similar pattern of ~17 kDa cleaved MUC16 was observed in multiple cell types eliminating the possibility of cell type specific phenomenon. MUC16-Cter translocates to the nucleus in a cleavage dependent manner and binds to the chromatin suggesting its involvement in regulation of gene expression. Taken together, we demonstrate for the first time the oft-predicted cleavage of MUC16 that is critical in designing successful therapeutic interventions based on MUC16.

Indexed as

Protein Interaction Domains and MotifsAnimalsCA-125 AntigenCell MembraneGlycosylationGolgi ApparatusHumansHydrogen-Ion ConcentrationIntracellular SpaceLeukocyte ElastaseMatrix Metalloproteinase 7Membrane ProteinsMiceProtein StabilityProtein TransportProteolysisCA-125 AntigenLeukocyte ElastaseMatrix Metalloproteinase 7Membrane ProteinsMUC16 protein, human

Identifiers

PMID26044153
PMCPMC4456727
OpenAlexW630438197

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.