The possible roles of B-cell novel protein-1 (BCNP1) in cellular signalling pathways and in cancer.
B-cell novel protein-1 (BCNP1) or Family member of 129C (FAM129C) was identified as a B-cell-specific plasma-membrane protein. Bioinformatics analysis predicted that BCNP1 might be heavily phosphorylated. The BCNP1 protein contains a pleckstrin homology (PH) domain, two proline-rich (PR) regions and a Leucine Zipper (LZ) domain suggesting that it may be involved in protein-protein interactions. Using The Cancer Genome Atlas (TCGA) data sets, we investigated the correlation of alteration of the BCNP1 copy-number changes and mutations in several cancer types. We also investigated the function of BCNP1 in cellular signalling pathways. We found that BCNP1 is highly altered in some types of cancers and that BCNP1 copy-number changes and mutations co-occur with other molecular alteration events for TP53 (tumour protein P53), PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase, Catalytic Subunit Alpha), MAPK1 (mitogen-activated protein kinase-1; ERK: extracellular signal regulated kinase), KRAS (Kirsten rat sarcoma viral oncogene homolog) and AKT2 (V-Akt Murine Thymoma Viral Oncogene Homolog 2). We also found that PI3K (Phoshoinositide 3-kinase) inhibition and p38 MAPK (p38 mitogen-activated protein kinase) activation leads to reduction in phosphorylation of BCNP1 at serine residues, suggesting that BCNP1 phosphorylation is PI3K and p38MAPK dependent and that it might be involved in cancer. Its degradation depends on a proteasome-mediated pathway.
Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY, USA.|Department of Chemistry and Biomolecular Science, Clarkson University, Biochemistry and Proteomics Group, Potsdam, NY, USA.
Sapan J
SJ
Patel
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Gaurang L
GL
Trivedi
Department of Chemistry and Biomolecular Science, Clarkson University, Biochemistry and Proteomics Group, Potsdam, NY, USA.
Costel C
0000-0001-6402-2311
CC
Darie
Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY, USA.
Bayard D
BD
Clarkson
D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D058534:Class I Phosphatidylinositol 3-Kinases; D056915:DNA Copy Number Variations / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D058534:Class I Phosphatidylinositol 3-Kinases; D008565:Membrane Proteins; D019950:Mitogen-Activated Protein Kinase 1; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D016283:Proto-Oncogene Proteins p21(ras); D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases; C117307:KRAS protein, human; C477321:NIBAN3 protein, human; C484760:PIK3CA protein, human; C494921:AKT2 protein, human; C535150:MAPK1 protein, human
B-cell novel protein-1; bioinformatics; family member of 129C; p38 MAPK; phoshoinositide 3-kinase
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