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

Harris, Janelle L., Richards, Renee S., Chow, Clement W. K., Lee, Soon, Kim, Misook, Buck, Marion, Teng, Linda, Clarke, Raymond, Gardiner, Robert A. and Lavin, Martin F. (2013) BMCC1 Is an AP-2 associated endosomal protein in prostate cancer cells. PloS One, 8 9: e73880.1-e73880.15. doi:10.1371/journal.pone.0073880

Author Harris, Janelle L.
Richards, Renee S.
Chow, Clement W. K.
Lee, Soon
Kim, Misook
Buck, Marion
Teng, Linda
Clarke, Raymond
Gardiner, Robert A.
Lavin, Martin F.
Title BMCC1 Is an AP-2 associated endosomal protein in prostate cancer cells
Journal name PloS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-09-01
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0073880
Open Access Status DOI
Volume 8
Issue 9
Start page e73880.1
End page e73880.15
Total pages 16
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Formatted abstract
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.
Keyword Clathrin Mediated Endocytosis
Homology Bch Domain
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
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Created: Sun, 27 Oct 2013, 10:13:47 EST by System User on behalf of UQ Centre for Clinical Research