Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.3.16 (
calcineurin
)
17,112
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Coenzyme Q
10
(CoQ
10
) is a redox molecule critical for the proper function of energy metabolism and antioxidant defenses. Despite its essential role in cellular metabolism, the regulation of CoQ
10
biosynthesis in humans remains mostly unknown. Herein, we determined that
PPTC7
is a regulatory protein of CoQ
10
biosynthesis required for human cell survival. We demonstrated by in vitro approaches that
PPTC7
is a bona fide
protein phosphatase
that dephosphorylates the human COQ7. Expression modulation experiments determined that human
PPTC7
dictates cellular CoQ
10
content. Using two different approaches (
PPTC7
over-expression and caloric restriction), we demonstrated that
PPTC7
facilitates and improves the human cell adaptation to respiratory conditions. Moreover, we determined that the physiological role of
PPTC7
takes place in the adaptation to starvation and pro-oxidant conditions, facilitating the induction of mitochondrial metabolism while preventing the accumulation of ROS. Here we unveil the first post-translational mechanism regulating CoQ
10
biosynthesis in humans and propose targeting the induction of
PPTC7
activity/expression for the treatment of CoQ
10
-related mitochondrial diseases.
...
PMID:The mitochondrial phosphatase PPTC7 orchestrates mitochondrial metabolism regulating coenzyme Q
10
biosynthesis. 3026 71
Protein phosphatases and kinases control multiple cellular events including proliferation, differentiation, and stress responses through regulating reversible protein phosphorylation, the most important post-translational modification. Members of metal-dependent
protein phosphatase
(PPM) family, also known as PP2C phosphatases, are Ser/Thr phosphatases that bind manganese/magnesium ions (Mn
2+
/Mg
2+
) in their active center and function as single subunit enzymes. In mammals, there are 20 isoforms of PPM phosphatases: PPM1A, PPM1B, PPM1D, PPM1E, PPM1F, PPM1G, PPM1H, PPM1J, PPM1K, PPM1L, PPM1M, PPM1N, ILKAP, PDP1, PDP2, PHLPP1, PHLPP2, PP2D1,
PPTC7
, and TAB1, whereas there are only 8 in yeast. Phylogenetic analysis of the DNA sequences of vertebrate PPM isoforms revealed that they can be divided into 12 different classes: PPM1A/PPM1B/PPM1N, PPM1D, PPM1E/PPM1F, PPM1G, PPM1H/PPM1J/PPM1M, PPM1K, PPM1L, ILKAP, PDP1/PDP2, PP2D1/PHLPP1/PHLPP2, TAB1, and
PPTC7
. PPM-family members have a conserved catalytic core region, which contains the metal-chelating residues. The different isoforms also have isoform specific regions within their catalytic core domain and terminal domains, and these regions may be involved in substrate recognition and/or functional regulation of the phosphatases. The twenty mammalian PPM phosphatases are involved in regulating diverse cellular functions, such as cell cycle control, cell differentiation, immune responses, and cell metabolism. Mutation, overexpression, or deletion of the PPM phosphatase gene results in abnormal cellular responses, which lead to various human diseases. This review focuses on the structures and biological functions of the PPM-phosphatase family and their associated diseases. The development of specific inhibitors against the PPM phosphatase family as a therapeutic strategy will also be discussed.
...
PMID:Metal-dependent Ser/Thr protein phosphatase PPM family: Evolution, structures, diseases and inhibitors. 3265 9
