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Gene Review

BIK  -  BCL2-interacting killer (apoptosis-inducing)

Homo sapiens

Synonyms: Apoptosis inducer NBK, BIP1, BP4, Bcl-2-interacting killer, NBK
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Disease relevance of BIK


High impact information on BIK

  • When expressed together, BIK and NOXA cause rapid release of mobilized cytochrome c and activation of caspases [6].
  • Endoplasmic reticulum BIK initiates DRP1-regulated remodelling of mitochondrial cristae during apoptosis [6].
  • Here, we show that BH3-only BIK activates this pathway at the ER in intact cells, resulting in mitochondrial fragmentation but little release of cytochrome c to the cytosol [6].
  • The BIK-induced transformations in mitochondria are dynamic in nature and involve DRP1-dependent remodelling and opening of cristae, where the major stores of cytochrome c reside [6].
  • Small interfering RNA (siRNA) suppression of p53 expression as well as overexpression of dominant-negative p53 effectively inhibited the fulvestrant induction of BIK mRNA, protein, and apoptosis [7].

Chemical compound and disease context of BIK


Biological context of BIK


Anatomical context of BIK


Associations of BIK with chemical compounds

  • Finally, Bik/NBK accumulation was caused by stabilization of the protein from degradation and was associated with bortezomib cytotoxicity and apoptosis induction [9].
  • Moreover, dramatic Bik/NBK accumulation and apoptosis induction were observed when cells were treated with proteasome inhibitor MG132 and calpain inhibitor I (ALLN) [9].
  • We show that BIK exists as a phosphoprotein and is phosphorylated at residues 33 (threonine) and 35 (serine) [3].
  • Mutation of the phosphorylation sites, in which the Thr and Ser residues were changed to alanine residues, reduced the apoptotic activity of BIK without significantly affecting its ability to heterodimerize with BCL-2 [3].
  • Fulvestrant neither affected the stability of the BIK mRNA transcripts [7].

Regulatory relationships of BIK

  • We show that this cell line expresses functional BAK protein and is defective in manifestation of apoptosis induced by the BH3-only proteins BIK and BID as well as extrinsic stimuli that engage the death receptors, tumor necrosis factor receptor, tumor necrosis factor-related apoptosis-inducing ligand receptor, and Fas [12].
  • BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria [13].
  • E1A depended on wild-type p53 to induce BIK and activate the death program [10].

Other interactions of BIK

  • Over-expression of p53 stimulates recruitment of BAK to the ER, and both its recruitment and assembly into higher order structures is inhibited by BIK small interfering RNA [14].
  • BIK, a BH (Bcl2 homology domain)3-only protein, is a proapoptotic member of the BCL2 family [1].
  • For example, a number of genes (BAD, BAK, BIK, and BAX) involved in apoptosis were found to be suppressed by methylation [15].
  • This benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone-insensitive pathway for stimulating cytochrome c release from mitochondria by ER BIK was successfully reconstituted in vitro and identified the requirement for components present in the light membrane (ER) and cytosol as necessary for this activity [13].

Analytical, diagnostic and therapeutic context of BIK


  1. Mutations of the BIK gene in human peripheral B-cell lymphomas. Arena, V., Martini, M., Luongo, M., Capelli, A., Larocca, L.M. Genes Chromosomes Cancer (2003) [Pubmed]
  2. A molecular analysis by gene expression profiling reveals Bik/NBK overexpression in sporadic breast tumor samples of Mexican females. García, N., Salamanca, F., Astudillo-de la Vega, H., Curiel-Quesada, E., Alvarado, I., Peñaloza, R., Arenas, D. BMC Cancer (2005) [Pubmed]
  3. Phosphorylation of the pro-apoptotic protein BIK: mapping of phosphorylation sites and effect on apoptosis. Verma, S., Zhao , L.J., Chinnadurai, G. J. Biol. Chem. (2001) [Pubmed]
  4. Epigenomic profiling reveals novel and frequent targets of aberrant DNA methylation-mediated silencing in malignant glioma. Kim, T.Y., Zhong, S., Fields, C.R., Kim, J.H., Robertson, K.D. Cancer Res. (2006) [Pubmed]
  5. Differentially expressed genes in hormone refractory prostate cancer: association with chromosomal regions involved with genetic aberrations. Stubbs, A.P., Abel, P.D., Golding, M., Bhangal, G., Wang, Q., Waxman, J., Stamp, G.W., Lalani, E.N. Am. J. Pathol. (1999) [Pubmed]
  6. Endoplasmic reticulum BIK initiates DRP1-regulated remodelling of mitochondrial cristae during apoptosis. Germain, M., Mathai, J.P., McBride, H.M., Shore, G.C. EMBO J. (2005) [Pubmed]
  7. Regulation of Expression of BIK Proapoptotic Protein in Human Breast Cancer Cells: p53-Dependent Induction of BIK mRNA by Fulvestrant and Proteasomal Degradation of BIK Protein. Hur, J., Bell, D.W., Dean, K.L., Coser, K.R., Hilario, P.C., Okimoto, R.A., Tobey, E.M., Smith, S.L., Isselbacher, K.J., Shioda, T. Cancer Res. (2006) [Pubmed]
  8. Nonapeptides selected by phage display mimic the binding sites of monoclonal antibodies BIP1 and BIP4 on Bet v 1, the major birch pollen allergen. Jensen-Jarolim, E., Ganglberger, E., Leitner, A., Radauer, C., Scheiner, O., Breiteneder, H. Int. Arch. Allergy Immunol. (1999) [Pubmed]
  9. Bik/NBK accumulation correlates with apoptosis-induction by bortezomib (PS-341, Velcade) and other proteasome inhibitors. Zhu, H., Zhang, L., Dong, F., Guo, W., Wu, S., Teraishi, F., Davis, J.J., Chiao, P.J., Fang, B. Oncogene (2005) [Pubmed]
  10. Induction and endoplasmic reticulum location of BIK/NBK in response to apoptotic signaling by E1A and p53. Mathai, J.P., Germain, M., Marcellus, R.C., Shore, G.C. Oncogene (2002) [Pubmed]
  11. 5-Aza-2'-deoxycytidine and depsipeptide synergistically induce expression of BIK (BCL2-interacting killer). Dai, Z., Liu, S., Marcucci, G., Sadee, W. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  12. Critical requirement of BAX for manifestation of apoptosis induced by multiple stimuli in human epithelial cancer cells. Theodorakis, P., Lomonosova, E., Chinnadurai, G. Cancer Res. (2002) [Pubmed]
  13. BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria. Germain, M., Mathai, J.P., Shore, G.C. J. Biol. Chem. (2002) [Pubmed]
  14. BH3-only BIK regulates BAX,BAK-dependent release of Ca2+ from endoplasmic reticulum stores and mitochondrial apoptosis during stress-induced cell death. Mathai, J.P., Germain, M., Shore, G.C. J. Biol. Chem. (2005) [Pubmed]
  15. Microarray analysis of epigenetic silencing of gene expression in the KAS-6/1 multiple myeloma cell line. Pompeia, C., Hodge, D.R., Plass, C., Wu, Y.Z., Marquez, V.E., Kelley, J.A., Farrar, W.L. Cancer Res. (2004) [Pubmed]
  16. Effect of postharvest storage on the expression of the apple allergen Mal d 1. Sancho, A.I., Foxall, R., Browne, T., Dey, R., Zuidmeer, L., Marzban, G., Waldron, K.W., van Ree, R., Hoffmann-Sommergruber, K., Laimer, M., Mills, E.N. J. Agric. Food Chem. (2006) [Pubmed]
  17. Monoclonal antibodies against birch pollen allergens: characterization by immunoblotting and use for single-step affinity purification of the major allergen Bet v I. Jarolim, E., Tejkl, M., Rohac, M., Schlerka, G., Scheiner, O., Kraft, D., Breitenbach, M., Rumpold, H. Int. Arch. Allergy Appl. Immunol. (1989) [Pubmed]
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