Biology subjects

Devillers, R.

Publications and source records attributed to Devillers, R..

3 recordsLinked to original sources

bioRxiv2026

ZNF768 regulates expression of E2F1 protein to drive G0/G1 transition and cell cycle progression.

Accurate and tightly coordinated cell cycle progression and cell proliferation are critical for development, growth and homeostasis of an organism. Recently, Zinc finger protein 768 (ZNF768) was identified as a transcription factor driving cellular proliferation, in both a p53-dependent and independent manner. ZNF768 interacts with and represses p53 functions to limit cell cycle delay. Independently, ZNF768 promotes the transcription of key regulators of the cell cycle machinery, although the mechanisms through which this occurs remain unknown. Here, we report that ZNF768 protein levels are tightly regulated during the cell cycle, and its depletion leads to cell cycle exit and induction of quiescence. We found that ZNF768 modulates the cell cycle, at least in part, by controlling expression of the major pro-proliferative transcription factor E2F1 independently of p53 activation. Consequently, depletion of ZNF768, which also represses expression of the key mitotic transcription factor and E2F1 target FOXM1, leads to numerous mitotic errors. Supporting these findings, cancer genomics analyses reveal that ZNF768 expression levels are positively associated with E2F1 and FOXM1 expression levels in human tumors, suggesting that cancer cells might use ZNF768 to override cell cycle arrest, sustain proliferation, and promote cancer progression. Altogether, our results reveal that ZNF768 modulates cell cycle entry and proliferation, at least in part by regulating E2F1 expression.

cell biology↗

bioRxiv2024

Social Anxiety Alters Theory of Mind Activation and Intersubject Neural Variability During Movie Viewing

Social anxiety is characterized by an intense fear of judgment in social situations, yet the underlying mechanisms driving this condition remain poorly understood. One hypothesis holds that specific alterations in Theory of Mind (ToM) affect the ability to interpret others thoughts and emotions. Another hypothesis proposes that broader interpretive biases lead individuals to perceive social cues as overly significant, even in neutral settings. We investigated these possibilities by measuring brain activity, pupil responses, and heart rates in socially anxious individuals and matched controls as they viewed Partly Cloudy, an animated film known to engage the ToM network during specific scenes. While overall brain activity during ToM-related scenes was similar across groups, socially anxious participants exhibited reduced activation in the left posterior superior temporal sulcus (pSTS), a key area for ToM processing. Additionally, intersubject correlation analysis revealed a distinct neural response pattern in the socially anxious group, marked by uniform responses in sensory regions and heightened variability in higher-order cortical areas. This pattern persisted throughout the film and occurred without changes in heart rate or pupil responses, indicating a neural processing bias that manifests even in non-evaluative settings. These findings provide a neural basis for ToM alterations and broader interpretive biases in social anxiety, supporting cognitive-behavioral models and suggesting novel targets for intervention.

neuroscience↗

bioRxiv2024

ARHGEF17/TEM4 regulates the cell cycle through control of G1 progression

The Ras homolog (Rho) small GTPases, via their role in regulating the actin cytoskeleton, coordinate diverse cellular functions including cell morphology, adhesion and motility, as well as cell cycle progression, survival and apoptosis. The upstream Rho regulators for many of these functions are unknown. ARHGEF17 (also known as TEM4) is a Rho family guanine nucleotide exchange factor (GEF) that been implicated in cell migration, cell-cell junction formation and the mitotic checkpoint. In this study we characterize the regulation of the cell cycle by TEM4. We demonstrate that TEM4 depleted cells exhibit multiple defects in mitotic entry and duration, spindle morphology, and spindle orientation. In addition, we find that TEM4 insufficiency leads to excessive cortical actin polymerization and cell rounding defects. Mechanistically, we demonstrate that TEM4 depleted cells delay in G1 as a consequence of elevated levels of the G1/S inhibitor p21waf1/cip1 and that TEM4 depleted cells that progress through to mitosis, do so with decreased transcription of CCNB1 and thus attenuated levels of cyclin B. Importantly, cyclin B overexpression in TEM4-depleted cells largely rescues mitotic progression and chromosome segregation defects in anaphase. Our study thus illustrates the consequences of Rho signalling imbalance on cell cycle progression and identifies TEM4 as the first GEF governing Rho GTPase-mediated regulation of G1/S.

cell biology↗