Promoter and Gene Structure
The human BOK promoter is activated by the overexpression of members of the E2F hand transcription factor family. Typically, these transcription factors are involved in the promotion of S-phase, so there might be a connection between Bok expression and cell cycle progression. Due to this regulation of Bok expression by the cell cycle, it was proposed that Bok sensitizes growing cells to stress-induced apoptosis.
Bok mRNA comprises five exons which code for a 213 amino acid protein, called Bok-L. This protein consists of four Bcl-2 homology domains (abbreviated BH1, BH2, BH3, BH4, respectively) and a C-terminal transmembrane region (Figure 1). Its BH3 domain contains a stretch with many leucine residues. This is unique among the Bcl-2 family members. The leucine-rich stretch functions as a nuclear export signal. It is recognized by the nuclear exportin Crm1. Mutations in the leucine-rich stretch impair the binding of Crm1 to Bok. Consequently, Bok accumulates in the nucleus and triggers apoptosis.
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—Paul Tillich (1886–1965)