Search results for "aggresome"
showing 8 items of 8 documents
Vitamin K3 chloro derivative (VKT-2) inhibits HDAC6, activates autophagy and apoptosis, and inhibits aggresome formation in hepatocellular carcinoma …
2020
Epigenetics plays a vital role in regulating gene expression and determining the specific phenotypes of eukaryotic cells. Histone deacetylases (HDACs) are important epigenetic regulatory proteins effecting multiple biological functions. Particularly, HDAC6 has become a promising anti-cancer drug target because of its regulation of cell mobility, protein trafficking, degradation of misfolded proteins, cell growth, apoptosis, and metastasis. In this study, we identified one out of six vitamin K3 derivatives, VKT-2, as HDAC6 inhibitor using molecular docking and cell viability assays in HDAC6-overexpressing HuH-7 cancer cells. Microscale thermophoresis and HDAC6 enzymatic assays revealed that …
BAG3 and friends: co-chaperones in selective autophagy during aging and disease.
2011
There is a reciprocal change in the expression of two members of the BAG (Bcl-2-associated athanogen) family, BAG1 and BAG3, during cellular aging and under acute stress ("BAG1-BAG3-switch"). BAG3 was recently described as a mediator of a novel macroautophagy pathway that uses the specificity of heat shock protein 70 (HSP70) to misfolded proteins and also involves other protein partners, such as HSPB8. Also crucial for induction and execution of autophagy are sequestosome-1/p62 (SQSTM1/p62) and LC3, an autophagosome-associated protein. In this novel pathway, BAG3 mediates the targeting and transport of degradation-prone substrates into aggresomes via the microtubule-motor dynein. Interestin…
The role of the co-chaperone BAG3 in selective macroautophagy: implications for aging and disease
2012
Maintenance of protein homeostasis, correct protein folding, refolding and clearance is of central importance for the function and survival of every cell. Here, the degradation of proteins is of particular importance, especially during aging and certain degenerative disorders when the protein load is increased. During cellular aging as well as under acute stress, there is a reciprocal change in expression of two members of the BAG (Bcl-2-associated athanogene) family, BAG1 and BAG3. While BAG1 serves an important function during the degradation of ubiquitinated proteins via the proteasome, BAG3 is the mediator of a novel macroautophagy pathway. This BAG3-mediated macroautophagy is based on …
The Cleavage Product of Amyloid-β Protein Precursor sAβPPα Modulates BAG3-Dependent Aggresome Formation and Enhances Cellular Proteasomal Activity
2015
Alzheimer's disease (AD) is the major age-associated form of dementia characterized by gradual cognitive decline. Aberrant cleavage of the amyloid-β protein precursor (AβPP) is thought to play an important role in the pathology of this disease. Two principal AβPP processing pathways exist: amyloidogenic cleavage of AβPP resulting in production of the soluble N-terminal fragment sAβPPβ, amyloid-β (Aβ), which accumulates in AD brain, and the AβPP intracellular domain (AICD) sAβPPα, p3 and AICD are generated in the non-amyloidogenic pathway. Prevalence of amyloidogenic versus non-amyloidogenic processing leads to depletion of sAβPPα and an increase in Aβ. Although sAβPPα is a well-accepted neu…
BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins.
2010
Increasing evidence indicates the existence of selective autophagy pathways, but the manner in which substrates are recognized and targeted to the autophagy system is poorly understood. One strategy is transport of a particular substrate to the aggresome, a perinuclear compartment with high autophagic activity. In this paper, we identify a new cellular pathway that uses the specificity of heat-shock protein 70 (Hsp70) to misfolded proteins as the basis for aggresome-targeting and autophagic degradation. This pathway is regulated by the stress-induced co-chaperone Bcl-2-associated athanogene 3 (BAG3), which interacts with the microtubule-motor dynein and selectively directs Hsp70 substrates …
BAG3 Proteomic Signature under Proteostasis Stress
2020
The multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3) represents a key player in the quality control of the cellular proteostasis network. In response to stress, BAG3 specifically targets aggregation-prone proteins to the perinuclear aggresome and promotes their degradation via BAG3-mediated selective macroautophagy. To adapt cellular homeostasis to stress, BAG3 modulates and functions in various cellular processes and signaling pathways. Noteworthy, dysfunction and deregulation of BAG3 and its pathway are pathophysiologically linked to myopathies, cancer, and neurodegenerative disorders. Here, we report a BAG3 proteomic signature under proteostasis stress. To elucidat…
Dendritic cell aggresome-like-induced structure formation and delayed antigen presentation coincide in influenza virus-infected dendritic cells.
2005
Abstract Influenza virus infection induces maturation of murine dendritic cells (DCs), which is most important for the initiation of an immune response. However, in contrast to EL-4 and MC57 cells, DCs present viral CTL epitopes with a delay of up to 10 h. This delay in Ag presentation coincides with the up-regulation of MHC class I molecules as well as costimulatory molecules on the cell surface and the accumulation of newly synthesized ubiquitinated proteins in large cytosolic structures, called DC aggresome-like-induced structures (DALIS). These structures were observed previously after LPS-induced maturation of DCs, and it was speculated that they play a role in the regulation of MHC cl…
The activation of aggresomal pathway in Coxsackievirus B3 infection
2016
Aggresomin muodostuminen on yksi solun puolustusmekanismeista, joka pyrkii estämään proteiinien haitallisen aggregoitumisen solulimassa. Aikaisemmat kokeet ovat näyttäneet, että ihmisen enterovirus-infektio aiheuttaa muutoksia vimentiinissä, tyypin III välikokoisessa filamentissa (Turkki et al., julkaisematon data). Nämä muutokset ovat hyvin samankaltaisia aggresomin muodostumisen aikana tapahtuvien muutoksien kanssa. Tämän tutkimuksen tarkoituksena oli selvittää mahdollisen aggresomin muodostumisreitin aktivoituminen Coxsackievirus B3 (CVB3) -infektiossa, ja hypoteesimme oli, että häkkimäisten vimentiinirakenteiden muodostumisen lisäksi myös muita aggresomin muodostumisreitin aktivoitumise…