Going Beyond Phosphorylation: Acetylphosphate-Mediated Ran Polymerase Acetylation and Caper Phosphorylation Co-Regulate Transcription of Escherichia Coli Stress-Responsive Gene cpxP

<p>The ability of bacteria to sense and adapt to environmental changes has al-lowed these organisms to thrive in all parts of the globe and to establish many complex interactions with the environments they live as well as other members of these environments. Crucial to monitoring extracellular conditions is a group of signaling pathways known as two-component signal transduction system (2CST). These systems relay information from the extracellular environment to the interior of the cell via a transfer of phosphoryl groups from the sensory protein know as sensor kinase (SK) to the output protein known as response regulator (RR).</p><p>In addition to this constant input of extracellular information, bacterial cells also monitor their intracellular environment, as among other things, it provides precious information about their nutritional status. It is the integration of these extracellular and intracellular cues that will determine which genes should be tran-scribed, assuring the most appropriate response for each environment at any given time.</p><p>Here, I present evidence that one of these 2CST systems in E. coli, the CpxAR system, integrates signals originated from both the extracellular environment and from central metabolic pathways to modulate transcription of the CpxR dependent gene cpxP. Through a series of genetic and biochemical experiments I demonstrate that acetyl-phosphate (AcP), a central metabolite originated from the Pta-AckA pathway, donates its phosphoryl group to the RR CpxR both in vitro and in vivo and that this transfer of phosphoryl group activates cpxP transcription.</p><p>In addition to CpxR phosphorylation, my data suggests that cpxP transcrip-tion is also sensitive to an additional posttranslational modification, N&#949;-lysine acety-lation of RNA polymerase (RNAP). My data implicate the acetylation of two lysine side chains on the carboxyl terminal domain of the &#945; subunit (&#945;CTD) of RNAP in the modulation of cpxP transcription in response to the AcP-dependent phosphorylation of CpxR. Together, CpxR phosphorylation and the acetylation of Lys-298 on &#945;CTD contribute to transcriptional activation of cpxP, whereas acetylation of Lys-291 dampens this response. Thus, protein phosphorylation and protein acetylation, seem to act together to fine-tune cpxP</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Microbiology and Immunology

Year dc:date.available

2013

Author dc:creator

• Lima, Bruno P.

• Acetylation
• Acetylphosphate
• RNA Polymerase
• Microbiology

Repository record dc:identifier

https://ecommons.luc.edu/luc_diss/676

OAI identifier oai:identifier

oai:ecommons.luc.edu:luc_diss-1675