Protein Degradation and the Pathologic Basis of Phenylketonuria and Hereditary Tyrosinemia.

International Journal of Molecular Sciences
Neha SarodayaSuresh Ramakrishna

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 in PAH and FAH gene, 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 pro...Continue Reading

References

Oct 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·B LindbladG Steen
Jul 18, 1981·Clinica Chimica Acta; International Journal of Clinical Chemistry·R BergerS K Wadman
Sep 1, 1981·Clinica Chimica Acta; International Journal of Clinical Chemistry·E A KvittingenO Stokke
Oct 6, 1997·Progress in Nucleic Acid Research and Molecular Biology·P BrossN Gregersen
Jul 25, 2000·The Journal of Biological Chemistry·M M JørgensenN Gregersen
Feb 7, 2001·The American Journal of Clinical Nutrition·F J van SpronsenP G Smit
Jun 19, 2001·Biochimica Et Biophysica Acta·A P Døskeland, T Flatmark
Mar 9, 2002·Science·F Ulrich Hartl, Manajit Hayer-Hartl
Mar 24, 2004·Seminars in Cell & Developmental Biology·José M BarralF Ulrich Hartl
Jun 3, 2004·Molecular Genetics and Metabolism·Nenad Blau, Heidi Erlandsen
Sep 17, 2005·Molecular Genetics and Metabolism·Christineh N Sarkissian, Alejandra Gámez
Jun 8, 2006·Annual Review of Biochemistry·Laurence H Pearl, Chrisostomos Prodromou
Apr 20, 2007·Human Mutation·Charles R Scriver
Jul 10, 2007·Journal of Inherited Metabolic Disease·J Gerard Loeber
Apr 11, 2008·Gene Therapy·I E AlexanderJ Christodoulou
Jun 10, 2008·American Journal of Human Genetics·Søren W GerstingAnia C Muntau
Dec 20, 2008·Proceedings of the National Academy of Sciences of the United States of America·Christineh N SarkissianCharles R Scriver
Jun 6, 2009·Nature Structural & Molecular Biology·F Ulrich Hartl, Manajit Hayer-Hartl
Dec 17, 2009·Orphanet Journal of Rare Diseases·David CassimanJaak Jaeken
Jun 10, 2010·Nature Reviews. Molecular Cell Biology·Mikko TaipaleSusan Lindquist
Sep 11, 2010·Nature·Byung-Hoon LeeDaniel Finley
Oct 15, 2010·Nature Reviews. Molecular Cell Biology·Jens TyedmersBernd Bukau
Apr 7, 2011·PLoS Biology·Robert ErnstHidde L Ploegh
Jul 13, 2011·Cold Spring Harbor Perspectives in Biology·Bryan ChenJudith Frydman
Jul 22, 2011·Nature·F Ulrich HartlManajit Hayer-Hartl
Sep 29, 2011·Biochimica Et Biophysica Acta·Jing LiJohannes Buchner
Jan 17, 2012·Seminars in Cell & Developmental Biology·Eric K Fredrickson, Richard G Gardner
May 31, 2012·Human Mutation·Christineh N SarkissianAurora Martinez
Jun 1, 2011·Therapeutic Advances in Endocrinology and Metabolism·Robin Lachmann
Nov 16, 2012·Current Pharmaceutical Design·Bindu NanduriMariola J Edelmann
Nov 30, 2012·Case Reports in Genetics·Jayesh J ShethFrenny J Sheth
Jan 24, 2013·Current Topics in Medicinal Chemistry·Jarl UnderhaugAurora Martinez
Mar 5, 2013·IUBMB Life·Marte I Flydal, Aurora Martinez
Mar 20, 2013·Trends in Biochemical Sciences·Alina RöhlJohannes Buchner
Feb 6, 2014·PLoS Genetics·Franziska KriegenburgRasmus Hartmann-Petersen

❮ Previous
Next ❯

Citations

Nov 22, 2020·International Journal of Molecular Sciences·Kamini KaushalSuresh Ramakrishna

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
protein folding
ubiquitination
deubiquitination
xenograft

Clinical Trials Mentioned

NCT03516487

Software Mentioned

Moderna

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Seminars in Cell & Developmental Biology
Heather L SmithMichael E Cheetham
The American Journal of Pathology
John HannaYagmur Micoogullari
Advances in Experimental Medicine and Biology
Catherine BoboriPanayiotis Vlamos
© 2021 Meta ULC. All rights reserved