Chaperone-mediated autophagy as a therapeutic target for parkinson disease. The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane. Macroautophagy is the most studied form of autophagy. 6 It is distinguished by its selectivity and the fact that, unlike the other two lysosomal pathways, it does not require vesicle formation substrate p. 188, 2339-2355.īandyopadhyay U., Kaushik S., Varticovski L. Chaperone-mediated autophagy is a form of selective autophagy which relies on the recognition of chaperons via targeted motif in the degrading proteins and lysosomal chaperons (45, 46). Chaperone-mediated autophagy (CMA) is a type of autophagy that is specialized in protein degradation and is based on the individual translocation of a cargo protein across the lysosomal membrane. Chaperone-mediated autophagy promotes beclin1 degradation in persistently infected hepatitis C virus cell culture. Cell 59, 270-284.Īydin Y., Stephens C.M., Chava S., Heidari Z., Panigrahi R., Williams D.D., Wiltz K., Bell A., Wilson W., Reiss K. Lysosomal mTORC2/PHLPP1/Akt regulate chaperone-mediated autophagy. Knockdown of the lysosomal CMA receptor LAMP2A increases protein levels of YAP1 and IL6ST, without changes in mRNA expression. 23, 184-189.Īrias E., Koga H., Diaz A., Mocholi E., Patel B. Here, we demonstrate that YAP1 and IL6ST are novel substrates of chaperone-mediated autophagy (CMA) in human hepatocellular carcinoma (HCC) and hepatocyte cell lines. The key players of chaperone-mediated autophagy (CMA), a particular. Chaperone-mediated autophagy in protein quality control. Evidence shows that chaperone-mediated autophagy (CMA) is involved in cancer cell pathogenesis and progression. Chaperone-Mediated Autophagy Markers LAMP2A and HSPA8 in Formalin-Fixed and. Here, we describe recent advances in the understanding of the molecular regulation of CMA, and discuss the evidence in support of the contribution of CMA dysfunction to cancers.Īrias E. The growing number of connections between CMA and cancers has generated interest in modulating CMA activity for therapeutic purposes. On the other hand, an anti-oncogenic role for CMA under physiological conditions in non-transformed cells is also proposed despite the pro-tumorigenic function of CMA in cancer cells. Recently, accumulating evidence has demonstrated a consistent increase in basal CMA activity in a wide array of cancer cell lines and human tumor biopsies, suggesting a potential link between CMA and cancer. The role of CMA in neurodegenerative diseases has been extensively studied in the past decades, with defects in the pathway being strongly associated with disease. Chaperone-mediated autophagy (CMA), a selective form of autophagy, where cellular proteins with KFERQ-like motif are targeted to the lysosome for degradation, is necessary to maintain cellular homeostasis.
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