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.

Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor PHA-848125

2012 ◽  
Vol 84 (5) ◽  
pp. 598-611 ◽  
Author(s):  
Simona Caporali ◽  
Ester Alvino ◽  
Lauretta Levati ◽  
Alessia I. Esposito ◽  
Marina Ciomei ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Down Regulation ◽  
Cyclin Dependent Kinase Inhibitor

scholarly journals MAD1 and p27KIP1 Cooperate To Promote Terminal Differentiation of Granulocytes and To Inhibit Myc Expression and Cyclin E-CDK2 Activity

2002 ◽  
Vol 22 (9) ◽  
pp. 3014-3023 ◽  
Author(s):  
Grant A. McArthur ◽  
Kevin P. Foley ◽  
Matthew L. Fero ◽  
Carl R. Walkley ◽  
Andrew J. Deans ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Activity ◽  
Kinase Inhibitor ◽  
Cyclin E ◽  
Null Alleles ◽  
Cyclin Dependent Kinase ◽  
Similar Treatment ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Cdk2 Activity ◽  
Differentiation Inducer

ABSTRACT To understand how cellular differentiation is coupled to withdrawal from the cell cycle, we have focused on two negative regulators of the cell cycle, the MYC antagonist MAD1 and the cyclin-dependent kinase inhibitor p27KIP1. Generation of Mad1/p27KIP1 double-null mice revealed a number of synthetic effects between the null alleles of Mad1 and p27KIP1, including embryonic lethality, increased proliferation, and impaired differentiation of granulocyte precursors. Furthermore, with granulocyte cell lines derived from the Mad1/p27KIP1 double-null mice, we observed constitutive Myc expression and cyclin E-CDK2 kinase activity as well as impaired differentiation following treatment with an inducer of differentiation. By contrast, similar treatment of granulocytes from Mad1 or p27KIP1 single-null mice resulted in differentiation accompanied by downregulation of both Myc expression and cyclin E-CDK2 kinase activity. In the double-null granulocytic cells, addition of a CDK2 inhibitor in the presence of differentiation inducer was sufficient to restore differentiation and reduce Myc levels. We conclude that Mad1 and p27KIP1 operate, at least in part, by distinct mechanisms to downregulate CDK2 activity and Myc expression in order to promote cell cycle exit during differentiation.

scholarly journals Down-regulation of the cyclin-dependent kinase inhibitor p57 is mediated by Jab1/Csn5 in hepatocarcinogenesis

Hepatology ◽  
2016 ◽  
Vol 63 (3) ◽  
pp. 898-913 ◽  
Author(s):  
Hui Guo ◽  
Li Jing ◽  
Yangzi Cheng ◽  
Vassilis Atsaves ◽  
Yi Lv ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Down Regulation ◽  
Cyclin Dependent Kinase Inhibitor

scholarly journals Heterologous expression of the human cyclin-dependent kinase inhibitor p21Cip1 in the fission yeast, Schizosaccharomyces pombe reveals a role for PCNA in the chk1+ cell cycle checkpoint pathway.

1996 ◽  
Vol 7 (4) ◽  
pp. 651-662 ◽  
Author(s):  
S Tournier ◽  
D Leroy ◽  
F Goubin ◽  
B Ducommun ◽  
J S Hyams
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Kinase Inhibitor ◽  
Binding Domain ◽  
Yeast Cells ◽  
Mutant Form ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Cell Cycle Inhibition ◽  
In Cells

Fission yeast cells expressing the human gene encoding the cyclin-dependent kinase inhibitor protein p21Cip1 were severely compromised for cell cycle progress. The degree of cell cycle inhibition was related to the level of p21Cip1 expression. Inhibited cells had a 2C DNA content and were judged by cytology and pulsed field gel electrophoresis to be in the G2 phase of the cell cycle. p21Cip1 accumulated in the nucleus and was associated with p34cdc2 and PCNA. Thus, p21Cip1 interacts with the same targets in fission yeast as in mammalian cells. Elimination of p34cdc2 binding by mutation within the cyclin-dependent kinase binding domain of p21Cip1 exaggerated the cell cycle delay phenotype. By contrast, elimination of PCNA binding by mutation within the PCNA-binding domain completely abolished the cell cycle inhibitory effects. Yeast cells expressing wild-type p21Cip1 and the mutant form that is unable to bind p34cdc2 showed enhanced sensitivity to UV. Cell cycle inhibition by p21Cip1 was largely abolished by deletion of the chk1+ gene that monitors radiation damage and was considerably enhanced in cells deleted for the rad3+ gene that monitors both DNA damage and the completion of DNA synthesis. Overexpression of PCNA also resulted in cell cycle arrest in G2 and this phenotype was also abolished by deletion of chk1+ and enhanced in cells deleted for rad3+. These results formally establish a link between PCNA and the products of the rad3+ and chk1+ checkpoint genes.

Sign in / Sign up

Export Citation Format

Share Document