CdcA1 Inhibitors

CdcA1, a conserved protein within the CDC48 family, plays a pivotal role in cell cycle regulation and protein degradation processes across various organisms. Primarily localized in the endoplasmic reticulum (ER), CdcA1 orchestrates ER-associated degradation (ERAD), ensuring the timely removal of misfolded or unassembled proteins. This essential function contributes to cellular homeostasis and quality control mechanisms, safeguarding against protein aggregation and cellular stress. Moreover, CdcA1's involvement in cell cycle progression underscores its significance in maintaining cellular integrity and viability. The inhibition of CdcA1 represents a critical avenue for modulating cellular processes associated with protein quality control and cell cycle regulation. Mechanistically, inhibition of CdcA1 disrupts the ERAD pathway, leading to accumulation of misfolded proteins within the ER lumen. This aberrant accumulation triggers unfolded protein response (UPR) pathways, activating stress sensors such as PERK, IRE1, and ATF6. Consequently, downstream signaling cascades are initiated to alleviate ER stress, which includes attenuation of protein translation, upregulation of chaperone expression, and induction of autophagy-mediated protein degradation. However, prolonged inhibition of CdcA1 may overwhelm cellular compensatory mechanisms, resulting in ER stress-induced apoptosis and cytotoxicity. Therefore, elucidating precise mechanisms of CdcA1 inhibition holds promise for understanding cellular responses to protein misfolding and ER stress, offering insights into disease pathogenesis.