| Description | A Bok transcript was initially isolated from a rat ovarian fusion cDNA library. Sequencing of this transcript has revealed that full-length BOK protein consists of 213 amino acids and contains three conserved BCL2 homology regions BH1, BH2, and BH3 in addition to a C-terminal transmembrane domain. BOK-S that results from the alternative splicing has its N-terminal BH3 domain part fused to the C-terminal part of the BH1 region. Using the yeast two-hybrid system, it has been demonstrated that, although the BH domains composition of BOK-L protein was similar to that of BAX and BAK, it interacted only with MCL-1, BHRF1, and BCL2A1/BFL-1 but not other anti-apoptotic multidomain BCL-2 family members. |
| Expression | Bok mRNA was isolated from the ovarian cDNA library. Results of Northern blot analysis revealed high expression levels of Bok mRNA in the reproductive tissues, such as ovary, testis, and uterus. Using in situ hybridization the authors localized Bok mRNA in granulosa cells. However, Bok expression is also evident in other mammalian tissues, such as brain, liver, thymus, lung, heart, kidney intestinal epithelium and lymphoid tissues. |
| Localisation | Intracellular localization of BOK protein remains to be clarified. Results of different studies suggest either its mitochondrial or cytosolic and nuclear localization. |
| Function | BOK promotes both caspase-dependent and caspase-independent apoptosis at the level of mitochondria in various cell types by promoting the release of pro-apoptotic mitochondrial factors to the cell cytosol. Inhibition of BOK induction using siRNA markedly decreases p53-dependent cell death. However, a specific mechanism, by which BOK increases mitochondrial membrane permeability, remains unknown. Apoptosis induced by BOK overexpression cannot be inhibited by Bcl-2 or Bcl-XL suggesting a unique role for BOK in apoptosis. A recent report indicates that BOK may cooperate with a BH3-only member, NOXA in p53-dependent apoptosis induced by DNA damage in human neuroblastoma cells, where it substitutes for a function of pro-apoptotic BAX. |
| Homology | Evolutionary conserved from fly to human. |
| Nuclear translocation of the pro-apoptotic Bcl-2 family member Bok induces apoptosis. |
| Bartholomeusz G, Wu Y, Ali Seyed M, Xia W, Kwong KY, Hortobagyi G, Hung MC |
| Molecular carcinogenesis. 2006 ; 45 (2) : 73-83. |
| PMID 16302269 |
| |
| Role of Mtd/Bok in normal and neoplastic B-cell development in the bursa of Fabricius. |
| Brown CY, Bowers SJ, Loring G, Heberden C, Lee RM, Neiman PE |
| Developmental and comparative immunology. 2004 ; 28 (6) : 619-634. |
| PMID 15177115 |
| |
| Loss of proapoptotic Bcl-2-related multidomain proteins in primary melanomas is associated with poor prognosis. |
| Fecker LF, Geilen CC, Tchernev G, Trefzer U, Assaf C, Kurbanov BM, Schwarz C, Daniel PT, Eberle J |
| The Journal of investigative dermatology. 2006 ; 126 (6) : 1366-1371. |
| PMID 16528364 |
| |
| Membrane translocation and oligomerization of hBok are triggered in response to apoptotic stimuli and Bnip3. |
| Gao S, Fu W, Dürrenberger M, De Geyter C, Zhang H |
| Cellular and molecular life sciences : CMLS. 2005 ; 62 (9) : 1015-1024. |
| PMID 15868100 |
| |
| The expression of Bok is regulated by serum in HC11 mammary epithelial cells. |
| Ha SH, Lee SR, Lee TH, Kim YM, Baik MG, Choi YJ |
| Molecules and cells. 2001 ; 12 (3) : 368-371. |
| PMID 11804337 |
| |
| A splicing variant of the Bcl-2 member Bok with a truncated BH3 domain induces apoptosis but does not dimerize with antiapoptotic Bcl-2 proteins in vitro. |
| Hsu SY, Hsueh AJ |
| The Journal of biological chemistry. 1998 ; 273 (46) : 30139-30146. |
| PMID 9804769 |
| |
| Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members. |
| Hsu SY, Kaipia A, McGee E, Lomeli M, Hsueh AJ |
| Proceedings of the National Academy of Sciences of the United States of America. 1997 ; 94 (23) : 12401-12406. |
| PMID 9356461 |
| |
| Mtd, a novel Bcl-2 family member activates apoptosis in the absence of heterodimerization with Bcl-2 and Bcl-XL. |
| Inohara N, Ekhterae D, Garcia I, Carrio R, Merino J, Merry A, Chen S, Nez G |
| The Journal of biological chemistry. 1998 ; 273 (15) : 8705-8710. |
| PMID 9535847 |
| |
| Bcl-2-related protein family gene expression during oligodendroglial differentiation. |
| Itoh T, Itoh A, Pleasure D |
| Journal of neurochemistry. 2003 ; 85 (6) : 1500-1512. |
| PMID 12787069 |
| |
| Bok, Bcl-2-related Ovarian Killer, Is Cell Cycle-regulated and Sensitizes to Stress-induced Apoptosis. |
| Rodriguez JM, Glozak MA, Ma Y, Cress WD |
| The Journal of biological chemistry. 2006 ; 281 (32) : 22729-22735. |
| PMID 16772296 |
| |
| BOK and NOXA are essential mediators of p53-dependent apoptosis. |
| Yakovlev AG, Di Giovanni S, Wang G, Liu W, Stoica B, Faden AI |
| The Journal of biological chemistry. 2004 ; 279 (27) : 28367-28374. |
| PMID 15102863 |
| |
| Evolutionarily conserved Bok proteins in the Bcl-2 family. |
| Zhang H, Holzgreve W, De Geyter C |
| FEBS letters. 2000 ; 480 (2-3) : 311-313. |
| PMID 11034351 |
| |
