page_title: CII protein
section_title: Function
hierarchical_section_title: CII protein / Function
caption_attribution_description: English: Lambda phage regulatory network: expression of cII
context_page_description: cII or transcriptional activator II is a DNA-binding protein and important transcription factor in the life cycle of lambda phage. It is encoded in the lambda phage genome by the 291 base pair cII gene. cII plays a key role in determining whether the bacteriophage will incorporate its genome into its host and lie dormant, or replicate and kill the host.
context_section_description: cII's primary role in the lambda phage regulatory network is to initiate the repressor establishment cascade. Once lysogeny is established, cII is no longer needed, and thus is turned off. It serves as the switch element for establishing repression of the lytic genes after infection, producing the lysogenic phenotype.
  cII is first expressed after phage protein N reaches sufficient levels to antiterminate the early right transcript past tR1, allowing RNA polymerase to transcribe the cII gene. If cII levels reach a certain threshold level, expression through the promoters pI, pRE and pAQ will be induced, initiating the two actions necessary in establishing lysogeny: 1) repression of lytic genes and 2) integration of the phage genome into the host's chromosome. Activation of promoter pRE enables expression of the repressor protein cI, which shuts off all lytic genes. pRE activation is also accompanied with a ~2 fold drop in pR activity due to convergent transcription of the two promoters, decreasing the expression of the lytic genes O and P. Activation of promoter pAQ produces the antisense RNA for Q, a key protein in the activation of the late lytic genes. Production of antisense Q RNA shuts off Q production, reducing lytic activity until the repressor cI can adequately shut off all lytic gene expression. Activation of the promoter pI causes the expression of the phage protein Int, whose role is to integrate the phage genome into the host's chromosome. Thus, although cII levels play a large role in determining the cell's fate, random thermal fluctuations also partially determine whether lysis or lysogeny is chosen.
  The level of cII in the cell during infection is highly variable due to its inherent in vivo instability, and its levels are highly influenced by environmental and cellular factors that influence its degradation rate. Such factors include temperature, cellular starvation and number of phage infecting the cell (an indication of population number of phage). Experiments have shown that low temperatures increase the in vivo half-life of cII from ~1-2 mins at 37˚C to 20 mins at 20˚C, thus increasing the probability of a cell to lysogenize. It is postulated that cII's increased stability at lower temperatures may be due to increased tetramerization and/or decreased Hfl-protease activity. Similarly, because host Hfl-proteases degrade proteins in an ATP dependent manner, coupling cII levels to Hfl-protease activity allows the bacteriophage to sense the energy status of the cell (healthy or starved). Thus lysogeny is favored when cells are starved. Finally, if a bacterial cell is infected by multiple bacteriophages, the level of cII increases due to additional contributions from each infecting phage. Lysogeny is therefore also favored in cells infected by multiple phages.
caption: Lambda phage regulatory network: expression of cII[3]
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