(Phospho)proteomic Profiling of Microsatellite Unstable CRC Cells Reveals Alterations in Nuclear Signaling and Cholesterol Metabolism Caused by Frameshift Mutation of NMD Regulator UPF3A.


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
23 Jul 2020
Historique:
received: 09 06 2020
revised: 13 07 2020
accepted: 20 07 2020
entrez: 29 7 2020
pubmed: 29 7 2020
medline: 17 2 2021
Statut: epublish

Résumé

DNA mismatch repair-deficient colorectal cancers (CRCs) accumulate numerous frameshift mutations at repetitive sequences recognized as microsatellite instability (MSI). When coding mononucleotide repeats (cMNRs) are affected, tumors accumulate frameshift mutations and premature termination codons (PTC) potentially leading to truncated proteins. Nonsense-mediated RNA decay (NMD) can degrade PTC-containing transcripts and protect from such faulty proteins. As it also regulates normal transcripts and cellular physiology, we tested whether NMD genes themselves are targets of MSI frameshift mutations. A high frequency of cMNR frameshift mutations in the

Identifiants

pubmed: 32718059
pii: ijms21155234
doi: 10.3390/ijms21155234
pmc: PMC7432364
pii:
doi:

Substances chimiques

Neoplasm Proteins 0
Phosphoproteins 0
RNA-Binding Proteins 0
UPF3A protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Deutsche Krebshilfe
ID : 592/6-2
Organisme : Deutsche Forschungsgemeinschaft
ID : 110121

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Auteurs

Malwina Michalak (M)

Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
Molecular Medicine Partnership Unit, Medical Faculty of the University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.

Eva-Maria Katzenmaier (EM)

Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
Molecular Medicine Partnership Unit, Medical Faculty of the University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany.

Nina Roeckel (N)

Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.

Stefan M Woerner (SM)

Molecular Medicine Partnership Unit, Medical Faculty of the University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany.
Department of Internal Medicine I, Endocrinology and Metabolism, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.

Vera Fuchs (V)

Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
Molecular Medicine Partnership Unit, Medical Faculty of the University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany.

Uwe Warnken (U)

Clinical Cooperation Unit Neurooncology, DKFZ (German Cancer Research Center), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Yan P Yuan (YP)

Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany.

Peer Bork (P)

Molecular Medicine Partnership Unit, Medical Faculty of the University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany.
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany.
Max-Delbrück-Centre for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany.

Gabriele Neu-Yilik (G)

Molecular Medicine Partnership Unit, Medical Faculty of the University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.

Andreas Kulozik (A)

Molecular Medicine Partnership Unit, Medical Faculty of the University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.

Magnus von Knebel Doeberitz (M)

Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
Molecular Medicine Partnership Unit, Medical Faculty of the University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany.
Clinical Cooperation Unit Applied Tumor Biology, DKFZ (German Cancer Research Center) Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Matthias Kloor (M)

Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
Molecular Medicine Partnership Unit, Medical Faculty of the University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany.
Clinical Cooperation Unit Applied Tumor Biology, DKFZ (German Cancer Research Center) Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Jürgen Kopitz (J)

Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
Molecular Medicine Partnership Unit, Medical Faculty of the University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany.
Clinical Cooperation Unit Applied Tumor Biology, DKFZ (German Cancer Research Center) Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Johannes Gebert (J)

Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
Molecular Medicine Partnership Unit, Medical Faculty of the University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany.
Clinical Cooperation Unit Applied Tumor Biology, DKFZ (German Cancer Research Center) Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

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Classifications MeSH