There are phage coded proteins and transcription factors [3–5] dedicated for this decision making process, but host factors are also involved [6–9]. Mutations in the cI, cII and cIII genes of λ [10] enhances the lytic Nutlin-3a mw frequency (leading to clear plaque formation, hence the names) and therefore the products of these genes were thought to be responsible for the establishment of lysogeny. CII, the key tetrameric transcription factor for lysogenic establishment, is a very unstable protein [7, 11, 12] and its presence in sufficient amounts is crucial for the lysogenic choice [13–15]. Other factors such as λCIII and the host

hfl proteins that influence the lysis-lysogeny switching affect the stability of CII in one way or the other. λCIII promotes lysogeny by acting as a general inhibitor of E. coli HflB that degrades CII [16]. Mutations in the host hfl loci cause an infecting λ particle to follow the lysogenic mode. Wortmannin clinical trial These genes therefore encode factors that somehow destabilize CII. Primarily from mutational studies, two such loci, hflA and hflB, were initially identified. The product of the latter gene, HflB, is an ATP-dependent metalloprotease known as a ‘quality control’ protease that removes misfolded proteins produced due to rapid translation during good nutrient conditions [17, 18]. CII is also

a substrate of HflB [7] and thus acts as a sensor for cellular nutrient conditions of the host. Rapid degradation of CII in cells growing in rich media thus favors the lytic development [13, 14]. The hflA locus consists of the genes hflX, hflK and hflC that are under the control of the same promoter [19–22]. Of these, AZD0156 mouse hflX has been demonstrated to have no role in lambda lysogeny [23]. The products see more of the other two, HflK and HflC, are tightly associated with each other and copurify as the ‘HflKC’ complex, which was earlier thought to

be a protease [24]. Subsequently, HflKC was found only to act as a ‘modulator’ of HflB by forming a complex with the latter [25–27]. The only other known E. coli factor in this process, HflD [9], has been shown to inhibit CII-mediated activation of transcription by impairing the DNA-binding ability of CII [28]. HflKC antagonizes the action of HflB towards the membrane associated substrates of the latter [18, 25]. The behavior of HflKC with respect to the cytosolic substrates of HflB (such as λCII), however, remains unclear. Likewise, the role of HflKC in the lysis-lysogeny decision of λ is not well understood. Though an ‘hfl’ protein, mutations in whose gene(s) causes an increase in the lysogenic frequency of λ [6], the deletion of these genes has little effect on the in vivo stability of exogenous CII [26]. CII expressed from a plasmid is found to be stabilized in an hflKC-deleted cell, only if the host is simultaneously infected with a lambda phage [26]. On the other hand, E. coli cells overexpressing HflKC exhibit an enhanced frequency of lysogenization [26].