The cyclin-dependent kinase inhibitor roscovitine inhibits kinase activity, cell proliferation, multicellular development, and Cdk5 nuclear translocation in Dictyostelium discoideum

2012 ◽  
Vol 113 (3) ◽  
pp. 868-876 ◽  
Author(s):  
Robert J. Huber ◽  
Danton H. O'Day
Keyword(s):  
Cell Proliferation ◽  
Dictyostelium Discoideum ◽  
Kinase Activity ◽  
Nuclear Translocation ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Multicellular Development ◽  
Cyclin Dependent Kinase Inhibitor

Myc Targets Cks1 To Provoke Proliferation and Lymphomagenesis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2618-2618
Author(s):  
Ulrich Keller ◽  
Jennifer B. Old ◽  
Jonas Nilsson ◽  
Lisa Nilsson ◽  
Kirsteen Maclean ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
Burkitt Lymphoma ◽  
Poor Prognosis ◽  
Transcriptional Activity ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Induced Apoptosis

Abstract Reduced levels of the cyclin dependent kinase inhibitor p27Kip1 connote poor prognosis in cancer. In human Burkitt lymphoma, and in pre-cancerous B cells and lymphomas arising in Eμ-Myc transgenic mice, p27Kip1 expression is markedly reduced. Furthermore, the Cks1 component of the SCFSkp2 complex that is necessary for p27Kip1 ubiquitylation and degradation, and to a lesser extent Skp2, are induced by Myc ex vivo and in Eμ-Myc B-cells and lymphomas, and up-regulation of CKS1 and SKP2 are hallmarks of Burkitt lymphoma. While loss of Skp2 has rather modest effects, the deletion of Cks1 in Eμ-Myc B-cells elevates p27Kip1 levels, reduces proliferation and delays lymphoma development. In contrast, Myc-induced apoptosis and transcriptional activity are not affected by Cks1 (or Skp2) loss. Therefore, Myc accelerates cell proliferation and promotes tumorigenesis through its ability to selectively induce Cks1.

scholarly journals Cyclin B Proteolysis and the Cyclin-dependent Kinase Inhibitor rum1p Are Required for Pheromone-induced G1 Arrest in Fission Yeast

1998 ◽  
Vol 9 (6) ◽  
pp. 1309-1321 ◽  
Author(s):  
Bodo Stern ◽  
Paul Nurse
Keyword(s):  
Fission Yeast ◽  
Kinase Activity ◽  
Kinase Inhibitor ◽  
Cyclin B ◽  
G1 Arrest ◽  
Cyclin Dependent Kinase ◽  
Down Regulation ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Pheromone Signaling

The blocking of G1 progression by fission yeast pheromones requires inhibition of the cyclin-dependent kinase cdc2p associated with the B-cyclins cdc13p and cig2p. We show that cyclosome-mediated degradation of cdc13p and cig2p is necessary for down-regulation of B-cyclin–associated cdc2p kinase activity and for phermone-induced G1 arrest. The cyclin-dependent kinase inhibitor rum1p is also required to maintain this G1arrest; it binds both cdc13p and cig2p and is specifically required for cdc13p proteolysis. We propose that rum1p acts as an adaptor targeting cdc13p for degradation by the cyclosome. In contrast, the cig2p–cdc2p kinase can be down-regulated, and the cyclin cig2p can be proteolyzed independently of rum1p. We suggest that pheromone signaling inhibits the cig2p–cdc2p kinase, bringing about a transient G1arrest. As a consequence, rum1p levels increase, thus inhibiting and inducing proteolysis of the cdc13p–cdc2p kinase; this is necessary to maintain G1 arrest. We have also shown that pheromone-induced transcription occurs only in G1 and is independent of rum1p.

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