Proteolysis dependent cell cycle regulation in Caulobacter crescentus

Abstract

Caulobacter crescentus, a Gram-negative alpha-proteobacterium, has surfaced as a powerful model system for unraveling molecular networks that control the bacterial cell cycle. A straightforward synchronization protocol and existence of many well-defined developmental markers has allowed the identification of various molecular circuits that control the underlying differentiation processes executed at the level of transcription, translation, protein localization and dynamic proteolysis. The oligomeric AAA+ protease ClpXP is a well-characterized example of an enzyme that exerts post-translational control over a number of pathways. Also, the proteolytic pathways of its candidate proteins are reported to play significant roles in regulating cell cycle and protein quality control. A detailed evaluation of the impact of its proteolysis on various regulatory networks of the cell has uncovered various significant cellular roles of this protease in C. crescentus. A deeper insight into the effects of regulatory proteolysis with emphasis on cell cycle progression could shed light on how cells respond to environmental cues and implement developmental switches. Perturbation of this network of molecular machines is also associated with diseases such as bacterial infections. Thus, research holds immense implications in clinical translation and health, representing a promising area for clinical advances in the diagnosis, therapeutics and prognosis.

Selectively advantageous instability in biotic and pre-biotic systems and implications for evolution and aging

“…Consistent with the importance of normally regulated cyclin degradation, mutations that increase the stability of cyclin D1 mRNA or protein promote cancer in mammals ( Chen and Li, 2022 ). Regulated protein degradation is also required for cell cycle progression in prokaryotes, including E. coli ( LaBreck et al, 2021 ) and Caulobacter crescentus ( Fatima et al, 2022 ). Cell division occurs in response to cell growth, which in turn can be considered a response to an appropriately nutrient-rich environment.…”

“…Self-assembly can be generally divided into two forms, static self-assembly and dynamic (dissipative) selfassembly. Static self-assembly is driven by the gain in free energy when the assembled structure represents a local or global minimum in the free energy landscape, resulting in a structure that is at equilibrium and stable with time (Fialkowski et al, 2006;Mattia and Otto, 2015). Examples of static self-assembly include crystals, lipid micelles (Alexandridis et al, 1994), and multi-subunit complexes such as HSF trimers (Kmiecik et al, 2020), and the nucleosome (Imbalzano et al, 1996;Langst and Becker, 2004;Becker and Workman, 2013).…”

“…Dynamic self-assembly requires a continuous source of energy in order to generate and maintain a functional structure that is far from equilibrium, and this energy is dissipated to the environment in a form such as heat (Fialkowski et al, 2006;Qian, 2006;Wagner and Pross, 2011;Maiti et al, 2016;Danger et al, 2020). Examples include actin filaments (Wear et al, 2000;Plastino and Blanchoin, 2018) and microtubules (Mitchison and Kirschner, 1984;Horio and Murata, 2014).…”

“…In bacteria, the conserved proteins FtsZ and FtsA dynamically assemble at the cell membrane at mid-cell location in a complex called the Z-ring, and regulate cytokinesis during cell division (Adams and Errington, 2009). For example, during the cell cycle of C. crescentus, synthesis and degradation of these proteins is regulated such that FtsZ peaks at middle S phase, and FtsA peaks at the S/G2 transition, reminiscent of eukaryotic cyclins (Fatima et al, 2022). In M. pneumoniae M129, both FtsZ and FtsA were found to be substrates of Lon, suggesting that Lon regulates Z-ring formation and disassembly and cytokinesis in this minimal cell (Burgos et al, 2020).…”

Integrative visualization of the molecular structure of a cellular microdomain

“…The AAA+ protease ClpXP degrades CtrA in a cell cycle‐dependent manner (Fatima et al, 2022 ; Joshi & Chien, 2016 ; Schroeder & Jonas, 2021 ). CpdR, RcdA, and the cdG receptor PopA are required for degradation of CtrA by ClpXP when bound to the chromosome.…”