Biology subjects

Hassan, F.

Publications and source records attributed to Hassan, F..

3 recordsLinked to original sources

bioRxiv2026

Distinct effects of Atg3 and Atg10 on Autophagosome Formation in Yeast

Autophagosome formation involves two E2 enzymes: Atg3, which conjugates Atg8 to the lipid phosphatidylethanolamine, and Atg10, which conjugates Atg12 to Atg5. Although both are required for autophagy, it is unclear exactly what roles these pathways play in the process of autophagosome formation. We used baker's yeast expressing mutant versions of both Atg3 and Atg10 that reduce, but do not eliminate, their activity to better understand their effects on Atg8 lipidation, autophagic flux, and the size and number of autophagosomes formed during nitrogen starvation. We found that while Atg3 primarily affects Atg8 lipidation and autophagosome size, Atg10 has less of an effect on Atg8 lipidation and primarily controls autophagosome number. This demonstrates that these two enzymes have distinct mechanistic roles in autophagosome formation, and implies an as-of-yet undiscovered function for the Atg12-Atg5 conjugate.

cell biology↗

bioRxiv2025

The fibrocystin C-terminal domain inhibits Src/STAT3 signal induced cystogenesis of kidney epithelia.

Autosomal recessive polycystic kidney disease (ARPKD) is caused by impaired function of fibrocystin/polyductin (FPC) in collecting duct epithelia resulting in cyst formation. We hypothesized that the membrane-bound C-terminal FPC domain (FPCct) is necessary to suppress cystogensis and facilitate epithelial homeostasis. In ARPKD, cystic kidney epithelia are characterized by a secretory phenotype associated with high intracellular cAMP levels and enhanced STAT3-dependent transcription. Moreover, impaired FPC function may lead to enhanced activation of Src tyrosine kinase, thereby activating STAT3 signaling and its downstream transcriptional activity. To investigate the effects of FPC loss on the cystic epithelial cell phenotype, we used an established principal-like MDCK cell line (pl-MDCK) and studied monolayers in both two and three-dimensional culture. In this in vitro model of collecting duct epithelia, FPC-deficient cells showed two-fold elevated basal cAMP levels and enhanced apical secretion leading to three-fold higher luminal pressure. Forskolin-stimulated elevation of cAMP levels triggered enhanced Src-dependent activation of STAT3 resulting in a pronounced cystic phenotype. Notably, expression of wildtype FPCct reduced both STAT3-dependent transcription and the secretory phenotype in knockout epithelial cells. Our data suggest that FPCct interacts with Src kinase at the plasma membrane, thereby reducing Src-mediated STAT3 phosphorylation and limiting STAT3-dependent transcription. Thus, FPCct appears to act like a physiological suppressor of cystogenic signaling, as found in healthy kidney epithelia, that is essential for maintaining epithelial homeostasis. Protein constructs that restore FPC C-terminal function may offer a therapeutic lead to mitigate epithelial dysfunction and slow disease progression in ARPKD.

cell biology↗

bioRxiv2023

Single-cell analysis characterizes PLK1 as a promoter of immunosuppressive tumor microenvironment in LUAD

PLK1 (Polo-like kinase 1) plays a critical role in the progression of lung adenocarcinoma (LUAD). Recent studies have unveiled that targeting PLK1 improves the efficacy of immunotherapy, highlighting its important role in the regulation of tumor immunity. Nevertheless, our understanding of the intricate interplay between PLK1 and the tumor microenvironment (TME) remains incomplete. Here, using genetically engineered mouse model and single-cell RNA-seq analysis, we report that PLK1 promotes an immunosuppressive TME in LUAD, characterized with enhanced M2 polarization of tumor associated macrophages (TAM) and dampened antigen presentation process. Mechanistically, elevated PLK1 coincides with increased secretion of CXCL2 cytokine, which promotes M2 polarization of TAM and diminishes expression of class II major histocompatibility complex (MHC-II) in professional antigen-presenting cells. Furthermore, PLK1 negatively regulates MHC-II expression in cancer cells, which has been shown to be associated with compromised tumor immunity and unfavorable patient outcomes. Taken together, our results reveal PLK1 as a novel modulator of TME in LUAD and provide possible therapeutic interventions.

cancer biology↗