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Effects of PGRMC1 phosphorylation on genome integrity and epigenetics

ABSTRACT: Progesterone receptor membrane component 1 (PGRMC1) is a protein that has been implicated in cancer biology and poor patient outcomes, which can be over-expressed in cancers, and exist in alternative states of phosphorylation.Here, we show that manipulation of PGRMC1 phosphorylation by mutagenesis results in altered cell metabolism. We examine the pathway by which nicotinamide-N-methyl transferase (NNMT) transfers a methyl group from S-adenosylmethionine (SAM) to produce 1-methylnicotinamide, lowering the levels of global methyl donor SAM. Hypothesizing that PGRMC1 phosphorylation status affects genome methylation, we discovered that each of several mutants elicited distinct patterns of CpG methylation.We conclude that PGRMC1 phosphorylation status, as controlled by unknown signaling processes, causes profound changes in cellular plasticity by affecting mechanisms also associated with early embryological tissue differentiation.

ORGANISM(S): Homo sapiens

SUBMITTER: Bashar Thejer

PROVIDER: E-MTAB-8218 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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