Glyceraldehyde 3-phosphate dehydrogenase is a SET-binding protein and regulates cyclin B-cdk1 activity.
We report here that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts in vitro and in vivo with the protein SET. This interaction is performed through the acidic domain of SET located at the carboxy terminal region. On analysing the functional relevance of SET-GAPDH interaction, we observed that GAPDH reverses in a dose-dependent manner, the inhibition of cyclin B-cdk1 activity produced by SET. Similarly to SET, GAPDH associates with cyclin B, suggesting that the regulation of cyclin B-cdk1 activity might be mediated not only by the interaction of GAPDH with SET but also with cyclin B. To analyse the putative role of GAPDH on cell cycle progression, HCT116 cells were transfected with a GAPDH expression vector. Results indicate that overexpression of GAPDH does not affect the timing of DNA replication but induces an increase in the number of mitosis, an advancement of the peak of cyclin B-cdk1 activity and an acceleration of cell cycle progression. All these results suggest that GAPDH might be involved in cell cycle regulation by modulating cyclin B-cdk1 activity.
Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
S
S
Carujo
J M
JM
Estanyol
A
A
Ejarque
N
N
Agell
O
O
Bachs
M J
MJ
Pujol
D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism*; D004261:DNA Replication / Q000235:genetics; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D005822:Genetic Vectors; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D056488:Histone Chaperones; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D002868:Chromosomal Proteins, Non-Histone; D019926:Cyclin B; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D009363:Neoplasm Proteins; C513473:SET protein, human; D014157:Transcription Factors; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D016203:CDC2 Protein Kinase