Switches and latches: a biochemical tug-of-war between the kinases and phosphatases that control mitosis

Domingo-Sananes, Maria Rosa; Kapuy, Orsolya; Hunt, Tim; Novák, Béla

doi:10.1098/rstb.2011.0087

Cited by 94 publications

(77 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, CDK1 is a master regulator of mitosis and is responsible for the phosphorylation of a large number of substrates (for a review, see Domingo-Sananes et al, 2011), FEN1 is essential for excision DNA repair (for a review, see Tsutakawa et al, 2011), and MATR3 and TDP-43 are RNA-binding proteins that regulate mRNA splicing and possibly other RNA metabolic processes (Coelho et al, 2015;Polymenidou et al, 2011). Partial loss of function of these activities and potentially many others could compromise cellular function or viability.…”

Section: Discussionmentioning

confidence: 99%

Vulnerability of newly synthesized proteins to proteostasis stress

Pattamatta

Hildago

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

The capacity of the cell to produce, fold and degrade proteins relies on components of the proteostasis network. Multiple types of insults can impose a burden on this network, causing protein misfolding. Using thermal stress, a classic example of acute proteostatic stress, we demonstrate that ∼5-10% of the soluble cytosolic and nuclear proteome in human HEK293 cells is vulnerable to misfolding when proteostatic function is overwhelmed. Inhibiting new protein synthesis for 30 min prior to heat-shock dramatically reduced the amount of heat-stress induced polyubiquitylation, and reduced the misfolding of proteins identified as vulnerable to thermal stress. Following prior studies in C. elegans in which mutant huntingtin (Q103) expression was shown to cause the secondary misfolding of cytosolic proteins, we also demonstrate that mutant huntingtin causes similar 'secondary' misfolding in human cells. Similar to thermal stress, inhibiting new protein synthesis reduced the impact of mutant huntingtin on proteostatic function. These findings suggest that newly made proteins are vulnerable to misfolding when proteostasis is disrupted by insults such as thermal stress and mutant protein aggregation.

show abstract

Section: Discussionmentioning

confidence: 99%

Vulnerability of newly synthesized proteins to proteostasis stress

Pattamatta

Hildago

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Cite this article as Cold Spring Harb Perspect Biol 2012;4:a005942 ensuring the commitment to mitosis that occurs at the G2/ M transition (Domingo-Sananes et al 2011). The regulation of protein subcellular localization, in addition to the regulation of protein activity, is important in the control of the G2/M transition.…”

Section: Control Of Cell Divisionmentioning

confidence: 99%

Signaling Pathways that Regulate Cell Division

Rhind

Russell

2012

Cold Spring Harbor Perspectives in Biology

143

117

View full text Add to dashboard Cite

SUMMARYCell division requires careful orchestration of three major events: entry into mitosis, chromosomal segregation, and cytokinesis. Signaling within and between the molecules that control these events allows for their coordination via checkpoints, a specific class of signaling pathways that ensure the dependency of cell-cycle events on the successful completion of preceding events. Multiple positive-and negative-feedback loops ensure that a cell is fully committed to division and that the events occur in the proper order. Unlike other signaling pathways, which integrate external inputs to decide whether to execute a given process, signaling at cell division is largely dedicated to completing a decision made in G1 phase-to initiate and complete a round of mitotic cell division. Instead of deciding if the events of cell division will take place, these signaling pathways entrain these events to the activation of the cell-cycle kinase cyclin-dependent kinase 1 (CDK1) and provide the opportunity for checkpoint proteins to arrest cell division if things go wrong.

show abstract

“…The various thresholds for cell cycle transitions are set by ratios of kinase activity to phosphatase activity and not by kinase activity per se. This theme continues in the contribution from Domingo-Sasanes et al [14], who restrict their discussion to the control of mitosis, but focus on the recently discovered role of greatwall kinase as a controller of protein phosphatases that both regulate and antagonize Cdks at the G2-M transition.…”

Section: Introductionmentioning

confidence: 99%