PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease.
Cell death
Cytochrome P450
Embryology
Epigenetics
Genomic sequence
Hyperspectral autofluorescence
Metabolism
Organizer
Steroid biology
Journal
BMC molecular and cell biology
ISSN: 2661-8850
Titre abrégé: BMC Mol Cell Biol
Pays: England
ID NLM: 101741148
Informations de publication
Date de publication:
15 Apr 2020
15 Apr 2020
Historique:
received:
18
12
2019
accepted:
20
03
2020
entrez:
16
4
2020
pubmed:
16
4
2020
medline:
30
12
2020
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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.
Identifiants
pubmed: 32293262
doi: 10.1186/s12860-020-00268-z
pii: 10.1186/s12860-020-00268-z
pmc: PMC7160964
doi:
Substances chimiques
Membrane Proteins
0
PGRMC1 protein, human
0
Receptors, Progesterone
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
26Subventions
Organisme : Charles Sturt University (AU)
ID : N/A
Organisme : Iraqi Cultural Attaché in Canberra (AUS)
ID : N/A
Organisme : Australian Research Council (AU)
ID : CE140100003
Organisme : Australian Research Council (AU)
ID : DE120102687
Organisme : Ramaciotti Foundations
ID : ES2012/0051
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