BioChem, Volume 3, Issue 4 (December 2023) – 3 articles

Signaling pathways that integrate a large set of inputs (both extra- and intracellular) to control cell proliferation are essential during both development and adult stages to guarantee organism homeostasis. Mobs are small adaptor proteins that participate in several of these signaling pathways. Here, we review recent advances unravelling Mob4 cellular functions, a highly conserved non-catalytic protein, that plays a diversity of roles in cell proliferation, sperm cell differentiation and is simultaneously involved in synapse formation and neural development. In addition, the gene is often overexpressed in a large diversity of tumors and is linked to poor clinical outcomes. Nevertheless, Mob4 molecular functions remain poorly defined, although it integrates the core structure of STRIPAK, a kinase/phosphatase protein complex, that can act upstream of the Hippo pathway. In this review we focus on the recent findings of Mob4 functions, that have begun to clarify its critical role on cell proliferation and the development of tissues and individuals. Full article

Diapause-like features can be extended to naïve mouse embryonic stem cells (mESCs) to induce paused pluripotency by using INK128 (mTi), a mammalian target of rapamycin (mTOR) inhibitor. As a core integrative pathway, mTOR senses diverse stimuli and translates these cues to coordinate several processes. We have previously shown that the withdrawal of leucine and arginine from the culture medium of naïve mESCs can induce features of a paused-pluripotent state, including reduced cell proliferation, cell cycle arrest, and reductions in glycolytic and oxidative metabolism. However, surprisingly, although mTi did indeed provoke a paused-like state, this was distinct from and less pronounced than what resulted from leucine and arginine removal, and, according to our results, these features did not seem to necessarily be mTOR-driven. Therefore, this possibility should be considered in further experiments, and mTOR inhibition when using INK128 should always be confirmed and not merely assumed when INK128 is present in the culture medium. Full article

A betel quid (BQ) chewing habit has been strongly associated with the development of several oral mucosal diseases. In order to investigate whether individual components of BQ mixtures have distinct physio-pathological effects on oral mucosal cells, we examined the impact of areca nut (AN), Piper betle leaf (Leaf), Piper betle stem inflorescence (SI), areca husk (Husk) and the complete BQ mixture on the growth of oral keratinocytes (OKF-6) and primary oral fibroblasts (MMF-1). Based on their known chemical properties, we selected BQ samples from Banda Aceh (BA) and West Papua (WP) regions for our in vitro study. We used a fluorescein diacetate assay (FDA) to assess the cell viability of BQ components on OKF-6 and MMF-1 cells. The cytotoxic effect of WP-AN on the OKF-6 cell line was observed at a concentration of 100 μg/mL, resulting in a 50% reduction in cell viability (IC50) after a 2-day incubation. Similarly, BA-AN exhibited cytotoxic effect, although at a higher concentration (500 μg/mL). WP-SI also displayed cytotoxic effects at a concentration of 500 μg/mL following 2 days of incubation. In contrast, Leaf, BQ mixture and husk extracts did not show any cytotoxic effects even after 3 days of incubation. No cytotoxic effects were observed at any concentration of BQ components when exposed to MMF-1 cells. Regarding cell proliferation, MMF-1 cells exposed to BA-AN and WP-AN showed increased growth on day 1, followed by decreased growth on day 2, in a dose- and time-dependent manner. Overall, our study indicates that BQ components induce distinctive cytotoxic effects on stromal and epithelial cells from the oral cavity. Full article