BMCC1 is an AP-2 associated endosomal protein in prostate cancer cells.

The prostate cancer antigen gene 3 (PCA3) is embedded in an intron of a second gene BMCC1 (Bcl2-/adenovirus E1B nineteen kDa-interacting protein 2 (BNIP-2) and Cdc42GAP homology BCH motif-containing molecule at the carboxyl terminal region 1) which is also upregulated in prostate cancer. BMCC1 was i...

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Autores principales: Janelle L Harris, Renée S Richards, Clement W K Chow, Soon Lee, Misook Kim, Marion Buck, Linda Teng, Raymond Clarke, Robert A Gardiner, Martin F Lavin
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:eec4dd42f8074044948b0fdd96a77d372021-11-18T08:56:29ZBMCC1 is an AP-2 associated endosomal protein in prostate cancer cells.1932-620310.1371/journal.pone.0073880https://doaj.org/article/eec4dd42f8074044948b0fdd96a77d372013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24040105/?tool=EBIhttps://doaj.org/toc/1932-6203The prostate cancer antigen gene 3 (PCA3) is embedded in an intron of a second gene BMCC1 (Bcl2-/adenovirus E1B nineteen kDa-interacting protein 2 (BNIP-2) and Cdc42GAP homology BCH motif-containing molecule at the carboxyl terminal region 1) which is also upregulated in prostate cancer. BMCC1 was initially annotated as two genes (C9orf65/PRUNE and BNIPXL) on either side of PCA3 but our data suggest that it represents a single gene coding for a high molecular weight protein. Here we demonstrate for the first time the expression of a >300 kDa BMCC1 protein (BMCC1-1) in prostate cancer and melanoma cell lines. This protein was found exclusively in the microsomal fraction and localised to cytoplasmic vesicles. We also observed expression of BMCC1 protein in prostate cancer sections using immunohistology. GST pull down, immunoprecipitation and mass spectrometry protein interaction studies identified multiple members of the Adaptor Related Complex 2 (AP-2) as BMCC1 interactors. Consistent with a role for BMCC1 as an AP-2 interacting endosomal protein, BMCC1 co-localised with β-adaptin at the perinuclear region of the cell. BMCC1 also showed partial co-localisation with the early endosome small GTP-ase Rab-5 as well as strong co-localisation with internalised pulse-chase labelled transferrin (Tf), providing evidence that BMCC1 is localised to functional endocytic vesicles. BMCC1 knockdown did not affect Tf uptake and AP-2 knockdown did not disperse BMCC1 vesicular distribution, excluding an essential role for BMCC1 in canonical AP-2 mediated endocytic uptake. Instead, we posit a novel role for BMCC1 in post-endocytic trafficking. This study provides fundamental characterisation of the BMCC1 complex in prostate cancer cells and for the first time implicates it in vesicle trafficking.Janelle L HarrisRenée S RichardsClement W K ChowSoon LeeMisook KimMarion BuckLinda TengRaymond ClarkeRobert A GardinerMartin F LavinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e73880 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Janelle L Harris
Renée S Richards
Clement W K Chow
Soon Lee
Misook Kim
Marion Buck
Linda Teng
Raymond Clarke
Robert A Gardiner
Martin F Lavin
BMCC1 is an AP-2 associated endosomal protein in prostate cancer cells.
description The prostate cancer antigen gene 3 (PCA3) is embedded in an intron of a second gene BMCC1 (Bcl2-/adenovirus E1B nineteen kDa-interacting protein 2 (BNIP-2) and Cdc42GAP homology BCH motif-containing molecule at the carboxyl terminal region 1) which is also upregulated in prostate cancer. BMCC1 was initially annotated as two genes (C9orf65/PRUNE and BNIPXL) on either side of PCA3 but our data suggest that it represents a single gene coding for a high molecular weight protein. Here we demonstrate for the first time the expression of a >300 kDa BMCC1 protein (BMCC1-1) in prostate cancer and melanoma cell lines. This protein was found exclusively in the microsomal fraction and localised to cytoplasmic vesicles. We also observed expression of BMCC1 protein in prostate cancer sections using immunohistology. GST pull down, immunoprecipitation and mass spectrometry protein interaction studies identified multiple members of the Adaptor Related Complex 2 (AP-2) as BMCC1 interactors. Consistent with a role for BMCC1 as an AP-2 interacting endosomal protein, BMCC1 co-localised with β-adaptin at the perinuclear region of the cell. BMCC1 also showed partial co-localisation with the early endosome small GTP-ase Rab-5 as well as strong co-localisation with internalised pulse-chase labelled transferrin (Tf), providing evidence that BMCC1 is localised to functional endocytic vesicles. BMCC1 knockdown did not affect Tf uptake and AP-2 knockdown did not disperse BMCC1 vesicular distribution, excluding an essential role for BMCC1 in canonical AP-2 mediated endocytic uptake. Instead, we posit a novel role for BMCC1 in post-endocytic trafficking. This study provides fundamental characterisation of the BMCC1 complex in prostate cancer cells and for the first time implicates it in vesicle trafficking.
format article
author Janelle L Harris
Renée S Richards
Clement W K Chow
Soon Lee
Misook Kim
Marion Buck
Linda Teng
Raymond Clarke
Robert A Gardiner
Martin F Lavin
author_facet Janelle L Harris
Renée S Richards
Clement W K Chow
Soon Lee
Misook Kim
Marion Buck
Linda Teng
Raymond Clarke
Robert A Gardiner
Martin F Lavin
author_sort Janelle L Harris
title BMCC1 is an AP-2 associated endosomal protein in prostate cancer cells.
title_short BMCC1 is an AP-2 associated endosomal protein in prostate cancer cells.
title_full BMCC1 is an AP-2 associated endosomal protein in prostate cancer cells.
title_fullStr BMCC1 is an AP-2 associated endosomal protein in prostate cancer cells.
title_full_unstemmed BMCC1 is an AP-2 associated endosomal protein in prostate cancer cells.
title_sort bmcc1 is an ap-2 associated endosomal protein in prostate cancer cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/eec4dd42f8074044948b0fdd96a77d37
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