Biology subjects

Muyan, M.

Publications and source records attributed to Muyan, M..

3 recordsLinked to original sources

bioRxiv2025

Yippee-like protein Moh1 links gene expression to metabolism and selective stress resistance in Saccharomyces cerevisiae

The Yippee-like (YPEL) proteins are a conserved eukaryotic gene family implicated in proliferation, senescence, and stress adaptation. In humans, five paralogs (YPEL1-YPEL5) are widely expressed and encode proteins with high sequence and amino acid similarity, yet the molecular basis of their functions remains poorly defined. While conservation implies possible functional redundancy, the distinct roles of each YPEL paralog have not been defined. The budding yeast S. cerevisiae possesses a single ortholog, MOH1, which contributes to survival and stress responses and can be functionally complemented by human YPELs. However, the cellular role of MOH1 remains to be elucidated. Here, we investigated the function of MOH1 in S. cerevisiae. MOH1 deletion (moh1{Delta}) conferred sensitivity to sodium azide and sulfuric acid but increased resistance to hydrogen peroxide and acetic acid. Moh1 protein levels decreased upon hydrogen peroxide treatment and increased following sulfuric acid exposure, indicating stress-dependent regulation. Light and scanning electron microscopy showed that moh1{Delta} cells are constitutively rounder, tend to form clumps, and exhibit rough surface features, indicating altered cellular architecture. RNA profiling and FTIR spectroscopy revealed transcriptional reprogramming and metabolic remodeling in moh1{Delta} cells, including alterations in lipid, protein, and cell wall polysaccharide levels and composition. Intracellular ROS assays indicated that hydrogen peroxide resistance can be attributed to decreased cellular uptake resulting from altered permeability, rather than changes in mitochondrial ROS production. Collectively, our findings identify Moh1 as a regulatory factor linking gene expression to metabolism and cellular architecture, influencing membrane permeability and conferring selective stress resistance in S. cerevisiae.

cell biology↗

bioRxiv2024

CXXC5 is a ubiquitinated protein and is degraded by the ubiquitination-proteasome pathway

CXXC5 as a member of the zinc-finger CXXC family proteins interacts with unmodified CpG dinucleotides to modulate the expression of genes involved in cellular proliferation, differentiation, and death in physiology and pathophysiology. Various signaling pathways including mitogenic estrogens, particularly 17{beta}-estradiol (E2), contribute to the expression and synthesis of CXXC5. However, how signaling pathways modulate protein levels of CXXC5 in cells is largely unknown. We previously reported that some key regulators, including retinoblastoma 1 and E74 Like ETS Transcription Factor 1, of the G1 to S phase transitions are involved in the expression of CXXC5 in estrogen-responsive MCF7 cells, derived from a breast adenocarcinoma. We, therefore, predict that the synthesis of CXXC5 is regulated in a cell cycle-dependent manner. We report here that although E2 in synchronized MCF7 cells augments both transcription and synthesis of CXXC5 in the G1 phase, CXXC5 protein levels are primarily mediated by ubiquitination independently of cell cycle phases. Utilizing the bioUbiquitination approach, which is based on cellular biotinylation of ubiquitin, in HEK293FT cells derived from immortalized human embryonic kidney cells followed by sequential immunoprecipitation coupled mass spectrometry analyses, we identified multiple ubiquitinated lysine residues of CXXC5. We show in both MCF7 and HEK293FT cells that the ubiquitinated lysine residues contribute to the degradation of CXXC5 through the ubiquitin-proteasome pathway.

cell biology↗

bioRxiv2023

Dynamic proximity interaction profiling suggests that YPEL2 is involved in cellular stress surveillance

YPEL2 is a member of the evolutionarily conserved YPEL family involved in cellular proliferation, mobility, differentiation as well as senescence and death. However, the mechanism by which YPEL2, or YPEL proteins, mediates its effects is yet unknown. Proteins perform their functions in a network of proteins whose identities, amounts, and compositions change spatiotemporally in a lineage-specific manner in response to internal and external stimuli. We here explored interaction partners of YPEL2 by using dynamic TurboID-coupled mass spectrometry analyses to infer a function for the protein. Our results using inducible transgene expressions in COS7 cells indicate that proximity interaction partners of YPEL2 are largely involved in RNA and mRNA metabolic processes, ribonucleoprotein complex biogenesis, regulation of gene silencing by miRNA, and cellular responses to stress. We showed that YPEL2 interacts with RNA binding protein ELAVL1 and selective autophagy receptor SQSTM1. We also found that YPEL2 participates in events associated with the formation/disassembly of stress granules in response to sodium arsenite an oxidative stress inducer. Establishing a point of departure in the delineation of structural/functional features of YPEL2, our results suggest that YPEL2 may be involved in stress surveillance mechanisms.

cell biology↗