Parkinson disease pathology often includes the presence of ubiquitin-positive, α-synuclein-enriched inclusions in the remaining neurons. Pink1 (also identified as PARK6) encodes a serinethreonine kinase involved in mitochondrial protection that works with parkin to ubiquitinate various proteins, promoting mitophagy. The parkin protein works to tag cystolic proteins for degradation, and previous...

Conformational diseases are associated with the conversion of normal proteins into aggregation-prone toxic conformers with structures similar to that of β-amyloid. Spatial distribution of amyloid-like proteins into intracellular quality control centers can be beneficial, but cellular mechanisms for protective aggregation remain unclear. We used a high-copy suppressor screen in yeast to identify...

background: candida albicans is one of the most important opportunistic pathogens that suppress immunologic mechanisms of the host. it is speculated that structural and secretory proteins of c. albicans have immunomodulatory effects in cancer. objective: to evaluate the effects of c. albicans structural and secreted proteins on intratumoral cd4/cd8 ratio as well as the survival rate in balb/c t...

The lethal factor (LF) and edema factor (EF) components of anthrax toxin are toxic to animal cells only if internalized by interaction with the protective antigen (PA) component. PA binds to a cell surface receptor and is proteolytically cleaved to expose a binding site for LF and EF. To study how LF and EF are internalized and trafficked within cells, LF was fused to the translocation and ADP-...

BACKGROUND There is a continuous demanding for tightly regulated prokaryotic expression systems, which allow functional synthesis of toxic proteins in Escherichia coli for bioscience or biotechnology application. However, most of the current promoter options either are tightly repressed only with low protein production levels, or produce substantial protein but lacking of the necessary repressi...

Secretory cargo that cannot fold properly in the ER are selectively targeted for removal by a well-studied ER-associated degradation pathway, or ERAD. In contrast, very little is known about post-ER quality control mechanisms for damaged or misfolded integral membrane proteins. Here we describe a quality control function of the Rsp5-ART ubiquitin ligase adaptor network that functions to protect...

Two proteins from parasporal crystals of Bacillus thuringiensis subsp. israelensis were purified to electrophoretic homogeneity by gel filtration and anion-exchange chromatography. The larger of the two proteins (molecular weight, 68,000) was not cytolytic, whereas the smaller protein (molecular weight, 28,000) was highly cytolytic when assayed against rat erythrocytes. When these proteins were...

When in the closed form, the substrate translocation channel of the proteasome core particle (CP) is blocked by the convergent N termini of α-subunits. To probe the role of channel gating in mammalian proteasomes, we deleted the N-terminal tail of α3; the resulting α3ΔN proteasomes are intact but hyperactive in the hydrolysis of fluorogenic peptide substrates and the degradation of polyubiquiti...

Intracellular synthesis, folding, trafficking and degradation of proteins are controlled and integrated by proteostasis. The frequency of protein misfolding disorders in the human population, e.g., in Alzheimer's disease (AD), is increasing due to the aging population. AD treatment options are limited to symptomatic interventions that at best slow-down disease progression. The key biochemical c...

The formation of protein aggregates is a hallmark neurodegenerative diseases. Observations on patient samples and model systems demonstrated links between aggregate declining mitochondrial functionality, but causalities remain unclear. We used Saccharomyces cerevisiae to analyze how processes regulate the behavior aggregation-prone polyQ derived from human huntingtin. Expression Q97-GFP rapidly...