Regulation of ubiquitous 6-phosphofructo-2-kinase by the ubiquitin-proteasome proteolytic pathway during myogenic C2C12 cell differentiation.
6-Phosphofructo-2-kinase catalyzes the synthesis and degradation of fructose 2,6-bisphosphate, activator of phosphofructokinase-1 and inhibitor of fructose 1,6-bisphosphatase. These properties confer to this bifunctional enzyme a key role in the control of glycolysis and gluconeogenesis. Several mammalian isozymes generated by alternative splicing from four genes, designated pfkfb1-4, have been identified. The results presented in this study demonstrate the expression of the pfkfb3 gene in C2C12 cells and its downregulation during myogenic cell differentiation. We also show that the decrease of ubiquitous 6-phosphofructo-2-kinase isozyme levels, product of pfkfb3 gene, is due to its enhanced degradation through the ubiquitin-proteasome proteolytic pathway.
Riera
Lluís
L
Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Campus de Bellvitge, Universitat de Barcelona, Feixa Llarga s/n, Pavelló de Govern, 4a planta E-08907 L'Hospitalet, Spain.
Obach
Mercè
M
Navarro-Sabaté
Aurea
A
Duran
Joan
J
Perales
Jose C
JC
Viñals
Francesc
F
Rosa
Jose Luis
JL
Ventura
Francesc
F
Bartrons
Ramon
R
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D025481:Phosphofructokinase-2 / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
D015853:Cysteine Proteinase Inhibitors; D007527:Isoenzymes; D007976:Leupeptins; D009097:Multienzyme Complexes; D011506:Proteins; D025801:Ubiquitin; C063261:acetylleucyl-leucyl-norleucinal; C107345:PFKFB3 protein, human; D025481:Phosphofructokinase-2; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex