The possible roles of B-cell novel protein-1 (BCNP1) in cellular signalling pathways and in cancer

J Cell Mol Med. 2017 Mar;21(3):456-466. doi: 10.1111/jcmm.12989. Epub 2016 Sep 29.

Abstract

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.

Keywords: B-cell novel protein-1; bioinformatics; family member of 129C; p38 MAPK; phoshoinositide 3-kinase.

MeSH terms

  • Apoptosis Regulatory Proteins
  • Cell Line
  • Class I Phosphatidylinositol 3-Kinases
  • DNA Copy Number Variations / genetics
  • HEK293 Cells
  • Humans
  • Membrane Proteins / genetics*
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mutation / genetics
  • Neoplasm Proteins / genetics*
  • Neoplasms / genetics*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphorylation / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Signal Transduction / genetics*
  • Tumor Suppressor Protein p53 / genetics
  • p38 Mitogen-Activated Protein Kinases / genetics

Substances

  • Apoptosis Regulatory Proteins
  • KRAS protein, human
  • Membrane Proteins
  • NIBAN3 protein, human
  • Neoplasm Proteins
  • Tumor Suppressor Protein p53
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • AKT2 protein, human
  • Proto-Oncogene Proteins c-akt
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • p38 Mitogen-Activated Protein Kinases
  • Proto-Oncogene Proteins p21(ras)