Autophagin

Last updated

Autophagin-1 (Atg4/Apg4) is a unique cysteine protease responsible for the cleavage of the carboxyl terminus of Atg8/Apg8/Aut7, a reaction essential for its lipidation during autophagy. [1] Human Atg4 homologues cleave the carboxyl termini of the three human Atg8 homologues, microtubule-associated protein light chain 3 (LC3), GABARAP, and GATE-16. [2]

Cysteine chemical compound

Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula HO2CCH(NH2)CH2SH. The thiol side chain in cysteine often participates in enzymatic reactions, as a nucleophile. The thiol is susceptible to oxidation to give the disulfide derivative cystine, which serves an important structural role in many proteins. When used as a food additive, it has the E number E920. It is encoded by the codons UGU and UGC.

Protease enzyme, type of hydrolase

A protease is an enzyme that catalyzes proteolysis, the breakdown of proteins into smaller polypeptides or single amino acids. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks bonds. Proteases are involved in many biological functions, including digestion of eaten proteins, protein catabolism, and cell signalling.

Autophagy cellular catabolic process in which cells digest parts of their own cytoplasm

Autophagy is the natural, regulated mechanism of the cell that removes unnecessary or dysfunctional components. It allows the orderly degradation and recycling of cellular components.

The rapid advancement in our understanding of the mechanisms and regulation of autophagy has placed this process in the center of current research in major human disorders. [3] The future challenge is to develop easy methods to separately manipulate the activity of each of the autophagic pathways. This would allow researchers to further understand their contribution to disease such as cancer, neurodegeneration, infectious disease, muscular disorders and possibly will provide therapeutic tools.

Cancer group of diseases

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans.

Neurodegeneration central nervous system disease

Neurodegeneration is the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases – including amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, and Huntington's disease – occur as a result of neurodegenerative processes. Such diseases are incurable, resulting in progressive degeneration and/or death of neuron cells. As research progresses, many similarities appear that relate these diseases to one another on a sub-cellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously. There are many parallels between different neurodegenerative disorders including atypical protein assemblies as well as induced cell death. Neurodegeneration can be found in many different levels of neuronal circuitry ranging from molecular to systemic.

See also

Related Research Articles

In cell biology, microtubule-associated proteins (MAPs) are proteins that interact with the microtubules of the cellular cytoskeleton.

ATG5 protein-coding gene in the species Homo sapiens

Autophagy related 5 (ATG5) is a protein that, in humans, is encoded by the ATG5 gene located on Chromosome 6. It is an E3 ubi autophagic cell death. ATG5 is a key protein involved in the extension of the phagophoric membrane in autophagic vesicles. It is activated by ATG7 and forms a complex with ATG12 and ATG16L1. This complex is necessary for LC3-I conjugation to PE (phosphatidylethanolamine) to form LC3-II. ATG5 can also act as a pro-apoptotic molecule targeted to the mitochondria. Under low levels of DNA damage, ATG5 can translocate to the nucleus and interact with survivin.

MAP1LC3B protein-coding gene in the species Homo sapiens

Microtubule-associated proteins 1A/1B light chain 3B is a protein that in humans is encoded by the MAP1LC3B gene. LC3 is a central protein in the autophagy pathway where it functions in autophagy substrate selection and autophagosome biogenesis. LC3 is the most widely used marker of autophagosomes.

MAP1LC3A protein-coding gene in the species Homo sapiens

Microtubule-associated proteins 1A/1B light chain 3A is a protein that in humans is encoded by the MAP1LC3A gene. Two transcript variants encoding different isoforms have been found for this gene.

ATG4B protein-coding gene in the species Homo sapiens

Cysteine protease ATG4B is an enzyme that in humans is encoded by the ATG4B gene.

GABARAPL2 protein-coding gene in the species Homo sapiens

Gamma-aminobutyric acid receptor-associated protein-like 2 is a protein that in humans is encoded by the GABARAPL2 gene.

ATG16L1 protein-coding gene in the species Homo sapiens

Autophagy related 16 like 1 is a protein that in humans is encoded by the ATG16L1 gene.

ATG12 protein-coding gene in the species Homo sapiens

Autophagy related 12 is a protein that in humans is encoded by the ATG12 gene.

ATG9A protein-coding gene in the species Homo sapiens

Autophagy-related protein 9A is a protein that in humans is encoded by the ATG9A gene.

ULK1 protein-coding gene in the species Homo sapiens

ULK1 is an enzyme that in humans is encoded by the ULK1 gene.

ATG7 protein-coding gene in the species Homo sapiens

Autophagy related 7 is a protein in humans encoded by ATG7 gene. Related to GSA7; APG7L; APG7-LIKE.

ATG4A protein-coding gene in the species Homo sapiens

Cysteine protease ATG4A is an enzyme that in humans is encoded by the ATG4A gene.

ATG8 fungal protein found in Saccharomyces cerevisiae S288c

Autophagy-related protein 8 (Atg8) is a ubiquitin-like protein required for the formation of autophagosomal membranes. The transient conjugation of Atg8 to the autophagosomal membrane through a ubiquitin-like conjugation system is essential for autophagy in eukaryotes. Even though there are homologues in animals, this article mainly focuses on its role in lower eukaryotes such as Saccharomyces cerevisiae.

AuTophaGy related 1 (Atg1) is a 101.7kDa serine/threonine kinase in S.cerevisiae, encoded by the gene ATG1. It is essential for the initial building of the autophagosome and Cvt vesicles. In a non-kinase role it is - through complex formation with Atg13 and Atg17 - directly controlled by the TOR kinase, a sensor for nutrient availability.

Autophagy-related protein 13 protein-coding gene in the species Homo sapiens

Autophagy-related protein 13 also known as ATG13 is a protein that in humans is encoded by the KIAA0652 gene.

An autophagosome is a spherical structure with double layer membranes. It is the key structure in macroautophagy, the intracellular degradation system for cytoplasmic contents. After formation, autophagosomes deliver cytoplasmic components to the lysosomes. The outer membrane of an autophagosome fuses with a lysosome to form an autolysosome. The lysosome's hydrolases degrade the autophagosome-delivered contents and its inner membrane.

In molecular biology, autophagy related 3 (Atg3) is the E2 enzyme for the LC3 lipidation process. It is essential for autophagocytosis. The super protein complex, the Atg16L complex, consists of multiple Atg12-Atg5 conjugates. Atg16L has an E3-like role in the LC3 lipidation reaction. The activated intermediate, LC3-Atg3 (E2), is recruited to the site where the lipidation takes place.

Yoshinori Ohsumi Japanese molecular biologist

Yoshinori Ohsumi is a Japanese cell biologist specializing in autophagy, the process that cells use to destroy and recycle cellular components. Ohsumi is a professor at Tokyo Institute of Technology's Institute of Innovative Research. He received the Kyoto Prize for Basic Sciences in 2012, the 2016 Nobel Prize in Physiology or Medicine, and the 2017 Breakthrough Prize in Life Sciences for his discoveries of mechanisms for autophagy.

References

  1. Development by self-digestion: molecular mechanisms and biological functions of autophagy by Levine B, Klionsky DJ. in Dev Cell. 2004 Apr;6(4):463-77. Review.
  2. HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubule-associated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates byTanida I, Sou YS, Ezaki J, Minematsu-Ikeguchi N, Ueno T, Kominami E. in J Biol Chem. 2004 Aug 27;279(35):36268-76
  3. Autophagy: in sickness and in health by Cuervo AM. in Trends Cell Biol. 2004 Feb;14(2):70-7.