Gankyrin is an ankyrin-repeat oncoprotein that interacts with CDK4 kinase and the S6 ATPase of the 26 S proteasome.
A yeast two-hybrid screen with the human S6 (TBP7, RPT3) ATPase of the 26 S proteasome has identified gankyrin, a liver oncoprotein, as an interacting protein. Gankyrin interacts with both free and regulatory complex-associated S6 ATPase and is not stably associated with the 26 S particle. Deletional mutagenesis shows that the C-terminal 78 amino acids of the S6 ATPase are necessary and sufficient to mediate the interaction with gankyrin. Deletion of an orthologous gene in Saccharomyces cerevisiae suggests that it is dispensable for cell growth and viability. Overexpression and precipitation of tagged gankyrin from cultured cells detects a complex containing co-transfected tagged S6 ATPase (or endogenous S6) and endogenous cyclin D-dependent kinase CDK4. The proteasomal ATPases are part of the AAA (ATPases associated with diverse cellular activities) family, members of which are molecular chaperones; gankyrin complexes may therefore influence CDK4 function during oncogenesis.
Dawson
Simon
S
Laboratory of Intracellular Proteolysis, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom. Simon.Dawson@nottingham.ac.uk
Apcher
Sebastien
S
Mee
Maureen
M
Higashitsuji
Hiroaki
H
Baker
Rohan
R
Uhle
Stefan
S
Dubiel
Wolfgang
W
Fujita
Jun
J
Mayer
R John
RJ
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D016296:Mutagenesis; D015513:Oncogene Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011518:Proto-Oncogene Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013379:Substrate Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D004268:DNA-Binding Proteins; D009097:Multienzyme Complexes; D015513:Oncogene Proteins; C403591:PSMD10 protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D003546:Cysteine Endopeptidases; C088863:PSMC4 protein, human; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities