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Protein Degradation and the Pathologic Basis of Phenylketonuria and Hereditary Tyrosinemia

Title
Protein Degradation and the Pathologic Basis of Phenylketonuria and Hereditary Tyrosinemia
Author
김계성
Keywords
deubiquitination; inhibitors; protein quality control; proteolysis; protein stabilization
Issue Date
2020-07
Publisher
SPANDIDOS PUBL LTD
Citation
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, v. 21, no. 14, article no. 4996
Abstract
A delicate intracellular balance among protein synthesis, folding, and degradation is essential to maintaining protein homeostasis or proteostasis, and it is challenged by genetic and environmental factors. Molecular chaperones and the ubiquitin proteasome system (UPS) play a vital role in proteostasis for normal cellular function. As part of protein quality control, molecular chaperones recognize misfolded proteins and assist in their refolding. Proteins that are beyond repair or refolding undergo degradation, which is largely mediated by the UPS. The importance of protein quality control is becoming ever clearer, but it can also be a disease-causing mechanism. Diseases such as phenylketonuria (PKU) and hereditary tyrosinemia-I (HT1) are caused due to mutations inPAHandFAHgene, resulting in reduced protein stability, misfolding, accelerated degradation, and deficiency in functional proteins. Misfolded or partially unfolded proteins do not necessarily lose their functional activity completely. Thus, partially functional proteins can be rescued from degradation by molecular chaperones and deubiquitinating enzymes (DUBs). Deubiquitination is an important mechanism of the UPS that can reverse the degradation of a substrate protein by covalently removing its attached ubiquitin molecule. In this review, we discuss the importance of molecular chaperones and DUBs in reducing the severity of PKU and HT1 by stabilizing and rescuing mutant proteins.
URI
https://www.mdpi.com/1422-0067/21/14/4996https://repository.hanyang.ac.kr/handle/20.500.11754/169333
ISSN
1422-0067
DOI
10.3390/ijms21144996
Appears in Collections:
GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S](의생명공학전문대학원) > BIOMEDICAL SCIENCE(의생명과학과) > Articles
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