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Title: Knockdown effects of CHIP and UCH-L1 on chaperone-mediated autophagy.
Authors: Tso, Rachel Ai Fang.
Keywords: DRNTU::Science
Issue Date: 2013
Abstract: Chaperone-mediated autophagy (CMA) is a selective form of autophagy which degrades cytosolic proteins bearing a CMA-targeting motif. CMA is carried out by chaperone proteins and aberrant CMA function has been implicated in disease. Its physiological regulation is not well understood, which is important for manipulating CMA in disease conditions. In this study, we explored plausible roles of ubiquitin-modifying enzymes in CMA. Previously, our lab detected polyubiquitinated proteins and ubiquitin-modifying enzymes in lysosomes that perform CMA. Such enzymes included CHIP (carboxyl terminus of Hsp70-interacting protein) and UCH-L1 (ubiquitin carboxy-terminal hydrolase L1). To investigate their functions, we examined their effects on CMA components. CMA-related chaperones bind and direct substrates to lysosomal membrane receptor LAMP-2A which subsequently multimerizes, creating a channel for substrates to enter lysosomes for degradation. Lysosomal membrane LAMP-2A levels directly correlate with CMA activity. We found that in SH-SY5Y cells depleted of CHIP or UCH-L1, some of the chaperones involved in CMA are affected. In particular, we observed a significant increase in LAMP-2A levels with a concomitant increase in LAMP-2A stability in both knockdown cells. Our results suggest that CHIP and UCH-L1 may influence CMA activity by modulating the levels of CMA chaperones and LAMP-2A in lysosomes.
Rights: Nanyang Technological University
Fulltext Permission: restricted
Fulltext Availability: With Fulltext
Appears in Collections:SBS Student Reports (FYP/IA/PA/PI)

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