Autophagin-1 (Atg4/Apg4) is a unique
cysteine protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the form ...
responsible for the cleavage of the
carboxyl terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain ( protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
of Atg8/Apg8/Aut7, a reaction essential for its lipidation during
autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent r ...
. Human Atg4 homologues cleave the carboxyl termini of the three human Atg8
homologues,
microtubule
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
-associated protein light chain 3 (LC3), GABARAP, and GATE-16.
The rapid advancement in our understanding of the mechanisms and regulation of
autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent r ...
has placed this process in the center of current research in major human disorders.
[Autophagy: in sickness and in health by Cuervo AM. in Trends Cell Biol. 2004 Feb;14(2):70-7.] 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
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
,
infectious disease
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...
, muscular disorders and possibly will provide therapeutic tools.
See also
*
Autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent r ...
*
Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes includ ...
*
Ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fou ...
References
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EC 3.4.22
Post-translational modification
Cellular processes