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2016 ; 17
(1
): 114-22
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Menin localization in cell membrane compartment
#MMPMID26560942
He X
; Wang L
; Yan J
; Yuan C
; Witze ES
; Hua X
Cancer Biol Ther
2016[]; 17
(1
): 114-22
PMID26560942
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Menin is encoded by the MEN1 gene, which is mutated in an inherited human
syndrome, multiple endocrine neoplasia type 1(MEN1). Menin is primarily nuclear
protein, acting as a tumor suppressor in endocrine organs, but as an oncogenic
factor in the mixed lineage leukemia, in a tissue-specific manner. Recently, the
crystal structures of menin with different binding partners reveal menin as a key
scaffold protein that functionally interacts with various partners to regulate
gene transcription in the nucleus. However, outside the nucleus, menin also
regulates multiple signaling pathways that traverse the cell surface membrane.
The precise nature regarding to how menin associates with the membrane fraction
is poorly understood. Here we show that a small fraction of menin associates with
the cell membrane fraction likely via serine palmitoylation. Moreover, the
majority of the membrane-associated menin may reside inside membrane vesicles, as
menin is protected from trypsin-mediated proteolysis, but disruption of the
membrane fraction using detergent abolishes the detection. Consistently, cellular
staining for menin also reveals the distribution of menin in the cell membrane
and the punctate-like cell organelles. Our findings suggest that part of
intracellular menin associates with the cell membrane peripherally as well as
resides within the membrane vesicles.
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