Abstract
In cells, protein synthesis and degradation are normal processes, which are tightly regulated by various cellular metabolic pathways. Cellular protein quality control (PQC) mechanisms always present a continuous and rigorous check over all intracellular proteins before they can participate in various cellular physiological processes with the help of PQC pathways like autophagy and ubiquitin proteasome system (UPS). The UPS employs few selective E3 ubiquitin ligases for the intracellular degradation of cyclin-dependent kinase inhibitor 1B (p27Kip1 ) that tightly controls cell cycle progression. But, the complex mechanistic interactions and the interplay between E3 ubiquitin ligases involved in the functional regulation as well as expression of p27 are not well known. Here, we demonstrate that cell surface glycoprotein Gp78, a putative E3 ubiquitin ligase, is involved in the stabilization of intracellular steady-state levels of p27. Transient overexpression of Gp78 increases the accumulation of p27 in cells in the form of massive inclusions like structures, which could be due to its cumulative increased stability in cells. We have also monitored how under stress condition, E3 ubiquitin ligase Gp78 regulates endogenous levels of p27 in cells. ER stress treatment generates a marginal increase in Gp78 endogenous levels, and this elevation effect was prominent for intracellular accumulation of p27 in cells. Taken together, our current findings suggest a valuable multifactorial regulatory mechanism and linkage of p27 with UPS pathway.