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PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease

BACKGROUND: Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissu...

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Autores principales: Thejer, Bashar M., Adhikary, Partho P., Teakel, Sarah L., Fang, Johnny, Weston, Paul A., Gurusinghe, Saliya, Anwer, Ayad G., Gosnell, Martin, Jazayeri, Jalal A., Ludescher, Marina, Gray, Lesley-Ann, Pawlak, Michael, Wallace, Robyn H., Pant, Sameer D., Wong, Marie, Fischer, Tamas, New, Elizabeth J., Fehm, Tanja N., Neubauer, Hans, Goldys, Ewa M., Quinn, Jane C., Weston, Leslie A., Cahill, Michael A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160964/
https://www.ncbi.nlm.nih.gov/pubmed/32293262
http://dx.doi.org/10.1186/s12860-020-00268-z
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author Thejer, Bashar M.
Adhikary, Partho P.
Teakel, Sarah L.
Fang, Johnny
Weston, Paul A.
Gurusinghe, Saliya
Anwer, Ayad G.
Gosnell, Martin
Jazayeri, Jalal A.
Ludescher, Marina
Gray, Lesley-Ann
Pawlak, Michael
Wallace, Robyn H.
Pant, Sameer D.
Wong, Marie
Fischer, Tamas
New, Elizabeth J.
Fehm, Tanja N.
Neubauer, Hans
Goldys, Ewa M.
Quinn, Jane C.
Weston, Leslie A.
Cahill, Michael A.
author_facet Thejer, Bashar M.
Adhikary, Partho P.
Teakel, Sarah L.
Fang, Johnny
Weston, Paul A.
Gurusinghe, Saliya
Anwer, Ayad G.
Gosnell, Martin
Jazayeri, Jalal A.
Ludescher, Marina
Gray, Lesley-Ann
Pawlak, Michael
Wallace, Robyn H.
Pant, Sameer D.
Wong, Marie
Fischer, Tamas
New, Elizabeth J.
Fehm, Tanja N.
Neubauer, Hans
Goldys, Ewa M.
Quinn, Jane C.
Weston, Leslie A.
Cahill, Michael A.
author_sort Thejer, Bashar M.
collection PubMed
description BACKGROUND: Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. RESULTS: Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture. CONCLUSIONS: A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.
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spelling pubmed-71609642020-04-22 PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease Thejer, Bashar M. Adhikary, Partho P. Teakel, Sarah L. Fang, Johnny Weston, Paul A. Gurusinghe, Saliya Anwer, Ayad G. Gosnell, Martin Jazayeri, Jalal A. Ludescher, Marina Gray, Lesley-Ann Pawlak, Michael Wallace, Robyn H. Pant, Sameer D. Wong, Marie Fischer, Tamas New, Elizabeth J. Fehm, Tanja N. Neubauer, Hans Goldys, Ewa M. Quinn, Jane C. Weston, Leslie A. Cahill, Michael A. BMC Mol Cell Biol Research Article BACKGROUND: Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. RESULTS: Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture. CONCLUSIONS: A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation. BioMed Central 2020-04-15 /pmc/articles/PMC7160964/ /pubmed/32293262 http://dx.doi.org/10.1186/s12860-020-00268-z Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Thejer, Bashar M.
Adhikary, Partho P.
Teakel, Sarah L.
Fang, Johnny
Weston, Paul A.
Gurusinghe, Saliya
Anwer, Ayad G.
Gosnell, Martin
Jazayeri, Jalal A.
Ludescher, Marina
Gray, Lesley-Ann
Pawlak, Michael
Wallace, Robyn H.
Pant, Sameer D.
Wong, Marie
Fischer, Tamas
New, Elizabeth J.
Fehm, Tanja N.
Neubauer, Hans
Goldys, Ewa M.
Quinn, Jane C.
Weston, Leslie A.
Cahill, Michael A.
PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
title PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
title_full PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
title_fullStr PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
title_full_unstemmed PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
title_short PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
title_sort pgrmc1 effects on metabolism, genomic mutation and cpg methylation imply crucial roles in animal biology and disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160964/
https://www.ncbi.nlm.nih.gov/pubmed/32293262
http://dx.doi.org/10.1186/s12860-020-00268-z
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