Disease relevance of Bik

• Untransfected melanoma cell lines expressed Nbk/Bik only weakly at the mRNA and protein level [1].
• Although systemically administered wild-type Bik significantly inhibited tumor growth and metastasis in an orthotopic nude mouse model, the proapoptotic potency of Bik can be modulated by posttranslational phosphorylation [2].
• Similarly, the synergy between bortezomib and TRAIL in killing human prostate cancer cells was impaired in cells in which both Bik and Bim were down-regulated by RNA interference [3].
• Furthermore, intratumoral injection of an adenovirus vector expressing the Bik gene, but not the deleted BH3 Bik gene, suppressed the growth of PC-3 and HT-29 xenografts established in nude mice [4].
• Expression of the death gene Bik/Nbk promotes sensitivity to drug-induced apoptosis in corticosteroid-resistant T-cell lymphoma and prevents tumor growth in severe combined immunodeficient mice [5].

High impact information on Bik

• Thus, Bik and Bim share, upstream of Bax, the role of eliminating supernumerary germ cells during the first wave of spermatogenesis, a process vital for normal testicular development [6].
• To investigate whether functional redundancy with Bim might obscure a significant role for Bik, we generated mice lacking both genes [6].
• We have determined the expression pattern in mice of the BH3-only protein Bik, also called Blk or Nbk, and examined its physiological function by gene targeting [7].
• These results indicate that any function of Bik in programmed cell death and stress-induced apoptosis must overlap that of other BH3-only proteins [7].
• We found that Bik is expressed widely in the hematopoietic compartment and in endothelial cells of the venous but not arterial lineages [7].

Biological context of Bik

• Concomitant loss of proapoptotic BH3-only Bcl-2 antagonists Bik and Bim arrests spermatogenesis [6].
• Loss of individual BH3-only proteins can lead either to no phenotype, as in mice lacking Bik, or to marked cell excess, as in the hematopoietic compartment of animals lacking Bim [6].
• As a model, we used the T-cell leukemia H9 (CD3(+) and CD4(+)CD8(-)), which is resistant to corticosteroid-induced cell death and does not express endogenous Bik/Nbk [5].
• The complete suppression of tumor growth in a severe combined immunodeficient mouse xenotransplant model suggests that, in analogy to Bax, Bik/Nbk may function as a tumor suppressor gene [5].
• Inspection of the human chromosome 22 syntenic region identified the proapoptotic Bik gene as a candidate [8].

Anatomical context of Bik

• However, although testes develop normally in mice lacking either Bik or Bim, adult bik-/-bim-/- males were infertile, with reduced testicular cellularity and no spermatozoa [6].
• This protein, designated Blk, is structurally and functionally related to human Bik and localized to the mitochondrial membrane [9].
• To determine whether the BH3 domain possesses a similar role in tumor tissues in vivo, we overexpressed the wild-type Bik protein and its BH3-deleted counterpart, using adenoviral technology, in chemoresistant human tumor prostate (PC-3) and colon (HT-29) cell lines growing in vitro and in vivo [4].
• Cutting edge: A/WySnJ transitional B cells overexpress the chromosome 15 proapoptotic Blk gene and succumb to premature apoptosis [8].

Associations of Bik with chemical compounds

• Significantly delayed tumor growth was the result when mice received doxycycline for induction of Nbk/Bik expression [1].
• Conditional expression of Nbk/Bik by applying the inducible tetracycline-responsive expression system triggered apoptosis and enhanced sensitivity to proapoptotic stimuli as to agonistic CD95 activation and to chemotherapeutics etoposide, doxorubicin and pamidronate [1].
• The increase in Bik levels seems to reflect inhibition by bortezomib of its proteasome-mediated degradation [3].

Physical interactions of Bik

• Blk contains a conserved BH3 domain and can interact with the anti-apoptotic proteins Bcl-2 and Bcl-xL [9].

Other interactions of Bik

• Therefore, we investigated whether the death-promoting Bcl-2 homologue Bik/Nbk can enhance cytostatic drug-induced apoptosis [5].

Analytical, diagnostic and therapeutic context of Bik

• Moreover, Bik mutant-liposome complexes inhibited tumor growth and prolonged life span more effectively than the wild-type Bik-liposome complex in an in vivo orthotopic animal model [2].

References