Role of Protein Phosphorylation in the Regulation of Cell Cycle and DNA-Related Processes in Bacteria

Abstract

In all living organisms, the phosphorylation of proteins modulates various aspects of their functionalities. In eukaryotes, protein phosphorylation plays a key role in cell signaling, gene expression, and differentiation. Protein phosphorylation is also involved in the global control of DNA replication during the cell cycle, as well as in the mechanisms that cope with stress-induced replication blocks. Similar to eukaryotes, bacteria use Hanks-type kinases and phosphatases for signal transduction, and protein phosphorylation is involved in numerous cellular processes. However, it remains unclear whether protein phosphorylation in bacteria can also regulate the activity of proteins involved in DNA-mediated processes such as DNA replication or repair. Accumulating evidence supported by functional and biochemical studies suggests that phospho-regulatory mechanisms also take place during the bacterial cell cycle. Recent phosphoproteomics and interactomics studies identified numerous phosphoproteins involved in various aspect of DNA metabolism strongly supporting the existence of such level of regulation in bacteria. Similar to eukaryotes, bacterial scaffolding-like proteins emerged as platforms for kinase activation and signaling. This review reports the current knowledge on the phosphorylation of proteins involved in the maintenance of genome integrity and the regulation of cell cycle in bacteria that reveals surprising similarities to eukaryotes.

Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity

“…Although the single phosphorylation cycle shows some ability to attenuate retroactivity, it is not able to transmit unidirectional signals due to the tradeoff seen above. We therefore study different architectures of signaling systems, composed of phosphorylation cycles and phosphotransfer systems that are ubiquitous in natural signal transduction ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 14 , 15 , 16 , 17 , 18 , 19 ). All reactions are modeled as two-step reactions.…”

“…Cellular signal transduction is typically viewed as a unidirectional transmission of information via biochemical reactions from an upstream system to multiple downstream systems through signaling pathways ( 1 , 2 , 3 , 4 , 5 , 6 , 7 ). However, without the presence of specialized mechanisms, signal transmission via chemical reactions is not in general unidirectional.…”

“…Phosphorylation-dephosphorylation (PD) cycles, phosphotransfer reactions, and cascades of these are ubiquitous in both prokaryotic and eukaryotic signaling pathways, playing a major role in cell cycle progression, survival, growth, differentiation and apoptosis ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 16 , 17 , 18 , 19 ). Numerous studies have been conducted to analyze such systems, starting with milestone works by Stadtman and Chock ( 20 , 21 , 22 ) and Goldbeter et al.…”

Computational study of the phosphoryl donor activity of dihydroxyacetone kinase from ATP to inorganic polyphosphate

“…In fact, one of the largest protein family of enzymes, namely kinases, catalyses the transfer of the terminal phosphate group from ATP to a substrate or other proteins . Different research works have been published about protein kinases where the phosphate from an ATP molecule is transferred mainly to a serine, threonine, or a tyrosine residue . From the mechanistic point of view, some authors describe phosphorylation reactions where a conserved aspartate residue acts as a base activating the acceptor residue, while others consider that this activation is caused by the ATP substrate itself .…”

Chromosome Segregation Proteins as Coordinators of Cell Cycle in Response to Environmental Conditions

“…Posttranslational modifications, especially phosphorylation, are well described mechanism to fine-tune the activity of the various proteins in response to changes of environmental conditions, e.g., nutrients availability (Stock et al, 1989;Bernal et al, 2014;Carabetta and Cristea, 2017;Janczarek et al, 2018). While number of nucleoid associated proteins (NAPs) including HU-like proteins were shown to be phosphorylated in B. subtilis and M. tuberculosis and plethora of DNA organizing proteins were suggested to be target for phosphorylation, the evidence for phosphorylation of chromosome segregation proteins is limited (Gupta et al, 2014;Garcia-Garcia et al, 2016). In mycobacteria, ParB was reported to be influenced by phosphorylation, which modified protein affinity toward DNA and abolished its interaction with ParA (Baronian et al, 2015).…”