Biology subjects

Marzoll, D.

Publications and source records attributed to Marzoll, D..

2 recordsLinked to original sources

bioRxiv2023

CK1δ homeostasis by activity-dependent shuttling and degradation of orphan kinase

Casein kinase 1{delta} (CK1{delta}) is a simple monomeric enzyme involved in the regulation of a variety of functions, including signal transduction, the circadian clock, and the cell cycle. Although CK1{delta} is targeted by the ubiquitin ligase APC/CCdh1 is not understood how CK1{delta} expression is regulated to support its multiple functions. Here, we show that kinase activity controls CK1{delta} homeostasis by coordinating two competing processes: export from the nucleus to ensure distribution of CK1{delta} between its assembly partners, and proteasomal degradation of unassembled CK1{delta} in the nucleus to keep the amount of active, potentially deleterious orphan kinase low. During mitosis, CK1{delta} is released from centrosomes and stabilized by (auto)phosphorylation to preserve it for the subsequent G1 phase. TeaserCompetitive nuclear export and nuclear degradation of active CK1{delta} ensure efficient partner interaction and keep unassembled kinase levels low.

biochemistry↗

bioRxiv2020

Multiple random phosphorylations provide long delays and switches in circadian clocks

Theory predicts that self-sustained oscillations require robust delays and nonlinearities (ultrasensitivity). Delayed negative feedback loops with switch-like inhibition of transcription constitute the core of eukaryotic circadian clock. The kinetics of core clock proteins such as PER2 in mammals and FRQ in Neurospora crassa is governed by multiple phosphorylations. We investigate how multiple, slow and random phosphorylations control delay and molecular switches. We model phosphorylations of intrinsically disordered clock proteins (IDPs) using conceptual models of sequential and distributive phosphorylations. Our models help to understand the underlying mechanisms leading to delays and ultrasensitivity. The model shows temporal and steady state switches for the free kinase and the phosphoprotein. We show that random phosphorylations and sequestration mechanisms allow high Hill coefficients required for self-sustained oscillations.

systems biology↗