Disease relevance of BIK

• Mutations of the BIK gene in human peripheral B-cell lymphomas [1].
• A molecular analysis by gene expression profiling reveals Bik/NBK overexpression in sporadic breast tumor samples of Mexican females [2].
• BIK complexes with various anti-apoptotic BCL-2 family proteins such as adenovirus E1B-19K and BCL-2 via the BH3 domain [3].
• Further characterization of 10 of these genes, including the putative metastasis suppressor CST6, the apoptosis-inducer BIK, and TSPYL5, whose function is unknown, revealed that they are frequent targets of epigenetic silencing in glioma cell lines and primary tumors and suppress glioma cell growth in culture [4].
• FN, BBC1, and UEV-1 localize to regions of chromosomal aberration (2q3.4, 16q24.3, and 20q13.2, respectively) associated with advanced prostate cancer and thus may be highly relevant to disease progression [5].

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

• Interestingly, other human breast cancer cells, such as ZR75-1, constitutively expressed BIK mRNA even without fulvestrant [7].
• Nonapeptides selected by phage display mimic the binding sites of monoclonal antibodies BIP1 and BIP4 on Bet v 1, the major birch pollen allergen [8].

Biological context of BIK

• Pretreatment of DLD1 cells with Bik/NBK siRNA reduced bortezomib-mediated Bik/NBK accumulation and cell death [9].
• Our results suggest that phosphorylation of BIK is required for eliciting efficient apoptotic activity [3].
• BIK function, however, was abrogated by a disabling point mutation within the BH3 domain [10].
• In summary, synergistic upregulation of pro-apoptotic BIK-previously shown to suppress tumor growth-appears to play a critical role in anticancer effects of 5-aza-2'-deoxycytidine plus depsipeptide [11].
• Histone acetylation of the BIK promoter region increased with depsipeptide treatment but was not further affected by 5-aza-2'-deoxycytidine [11].

Anatomical context of BIK

• The result showed that bortezomib induced rapid accumulation of Bik/NBK but not other Bcl-2 family members in all six cell lines [9].
• Bortezomib-mediated Bik/NBK accumulation and apoptosis were also observed in human embryonic kidney cells 293 and normal human bronchial epithelial cells [9].
• Partial purification of the protein kinase from HeLa cell cytoplasmic extracts suggest that BIK may be phosphorylated by a casein kinase II-related enzyme [3].

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

• A DNA microarray analysis identified the BH3-only BCL-2 family member, BIK/NBK, as a transcript that is upregulated during induction of apoptosis by oncogenic E1A [10].
• BIK induction was confirmed by RT-PCR and Western blots [11].
• A competitive enzyme-linked immunosorbent assay (ELISA) has been developed to determine Mal d 1 levels in apple pulp using a monoclonal antibody (BIP-1) [16].
• Two-dimensional electrophoresis/immunoblotting experiments revealed that BIP 1 reacted with all Bet v I isoallergens, also identified by human IgE antibodies [17].
• Using BIP 1 coupled to Sepharose 4B as reverse immunosorbent, Bet v I was obtained in a single-step procedure and characterized as single band by SDS-PAGE [17].

References