Repression Direct

Penicillins, like most antibiotics, are secondary products whose synthesis is not directly linked to growth. The enzymes that produce secondary products are normally repressed or inhibited under conditions which favour rapid growth. In the early work on penicillin, Penicillium rwtatum was grown as a floating mycelium on about 2 cm depth of liquid medium. The mycelium absorbed nutrients from the medium and penicillin was excreted into the medium. The mycelium and spent medium are readily separated. 

Muliprotein complexes that do not directly bind DNA, but are recruited by sequence-specific transcription factors and mediate their capacity to activate genes (coactivators) and to repress genes (corepressors). 

Desulfurization using cell-free extracts The first report of desulfurization by cell-free extract of R. erythropolis was by Ohshiro et al. [180], This report showed stoichiometric desulfurization of DBT by a cell-free system and identified NADH as a necessary co-factor for desulfurization. Subsequently, the enzyme activity of cell-free extracts of the strain R. erythropolis D-l was found to be inhibited by a 2-HBP, and its analog 2,2 -dihydroxybiphenyl (DBHP). Sulfate did not inhibit enzyme activity [90], further proving that its role is not in controlling enzyme activity directly but via a genetic repression mechanism as indicated above. 

The detailed mechanisms involved in CREB phosphorylation were first established for the cAMP pathway. A first messenger that increases cAMP concentrations leads to activation of PKA and to translocation of the free catalytic subunit of the protein kinase into the nucleus, where it phosphorylates CREB on serine 133. Such phosphorylation then promotes the binding of CREB to a CREB-binding protein (CBP). CBP, upon binding CREB, interacts directly with the RNA polymerase II complex, which mediates the initiation of transcription. In most cases, such interactions lead to the activation of transcription, although it is possible that the expression of some genes may be repressed. 

If these results suggest a positive role for nucleolin on proliferation, they do not indicate which of its activities are responsible for it. One hypothesis is that the stimulation of ribosome biogenesis by nucleolin is indispensable for active cell division. Indeed, a direct link between protein translation and cancer is clearly emerging (Ruggero and Pandolfi, 2003). However the studies mentioned above suggest a more direct impact of nucleolin on cell division. If part of its effects could come from its capacity to repress p53 mRNA translation (Takagi et al, 2005), a more direct role of nucleolin in DNA replication can also be considered. 

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