Analysis of nuclear high mobility group box 1 (HMGB1)-binding proteins in colon cancer cells: clustering with proteins involved in secretion and extranuclear function
- Analysis of nuclear high mobility group box 1 (HMGB1)-binding proteins in colon cancer cells: clustering with proteins involved in secretion and extranuclear function
- 이한나; 신나라; 송미영; 강운범; 염정훈; 이철주; 안영희; 유종신; 백영기; 김호근
- HMGB1; binding proteins; secretion
- Issue Date
- Journal of proteome research
- VOL 9, NO 9, 4661-4670
- HMGB1 is a nuclear protein that is overexpressed and secreted in cancer cells. However, little is known
about the roles of HMGB1 in the cytoplasm and secretory pathway in cancer cells. To clarify this aspect
of HMGB1 function, we fractionated the cytoplasm of HCT116 colon cancer cells and used a proteomic
approach to analyze cytoplasmic HMGB1-binding proteins. Pull-down experiments using recombinant
HMGB1 protein as bait, followed by mass spectrometry analysis identified 162 interacting proteins.
Among them were 74 proteins known to be localized exclusively to the extra-nuclear region, and 60
proteins known to be localized to both nuclear and extranuclear regions. The functions of these binding
proteins include involvement in cell-cycle progression, cell proliferation, anti-apoptosis, and angiogenesis.
In addition, nine of the identified proteins are related to protein translocation and secretion.
These include annexin A2, myosin IC isoform a, myosin-9, and Ras-related protein Rab10, which are
involved in unconventional protein secretion. Cytoplasmic HMGB1 was primarily associated with the
lysosomal cytosol fraction and was colocalized with the lysosomal marker LAMP1. Our findings suggest
that cytoplasmic HMGB1 binds to a number of molecules related to cancer progression and the
unconventional secretory pathway.
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