scholarly journals The Nucleocapsid Protein of Severe Acute Respiratory Syndrome-Coronavirus Inhibits the Activity of Cyclin-Cyclin-dependent Kinase Complex and Blocks S Phase Progression in Mammalian Cells

2006 ◽  
Vol 281 (16) ◽  
pp. 10669-10681 ◽  
Author(s):  
Milan Surjit ◽  
Boping Liu ◽  
Vincent T. K. Chow ◽  
Sunil K. Lal
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Nucleocapsid Protein ◽  
Mammalian Cells ◽  
S Phase ◽  
Cyclin Dependent Kinase ◽  
Phase Progression

scholarly journals WAF1 retards S-phase progression primarily by inhibition of cyclin-dependent kinases.

1997 ◽  
Vol 17 (8) ◽  
pp. 4877-4882 ◽  
Author(s):  
V V Ogryzko ◽  
P Wong ◽  
B H Howard
Keyword(s):  
Mammalian Cells ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
S Phase ◽  
In Vivo Studies ◽  
Nuclear Antigen ◽  
Phase Progression

The p21(WAF1/CIP1/sdi1) gene product (WAF1) inhibits DNA replication in vitro (J. Chen, P. Jackson, M. Kirschner, and A. Dutta, Nature 374:386-388, 1995; S. Waga, G. Hannon, D. Beach, and B. Stillman, Nature 369:574-578, 1994), but in vivo studies on the antiproliferative activity of WAF1 have not resolved G1-phase arrest from potential inhibition of S-phase progression. Here, we demonstrate that elevated WAF1 expression can retard replicative DNA synthesis in vivo. The WAF1-mediated inhibitory effect could be antagonized by cyclin A, cyclin E, or the simian virus 40 small-t antigen with no decrease in the levels of WAF1 protein in transfected cells. Proliferating-cell nuclear antigen (PCNA) overexpression was neither necessary nor sufficient to antagonize WAF1 action. Expression of the N-terminal domain of WAF1, responsible for cyclin-dependent kinase (CDK) interaction, had the same effect as full-length WAF1, while the PCNA binding C terminus exhibited modest activity. We conclude that S-phase progression in mammalian cells is dependent on continuing cyclin and CDK activity and that WAF1 affects S phase primarily through cyclin- and CDK-dependent pathways.

scholarly journals The Rice Cyclin-Dependent Kinase –Activating Kinase R2 Regulates S-Phase Progression

2002 ◽  
Vol 14 (1) ◽  
pp. 197-210 ◽  
Author(s):  
Tanja Fabian-Marwedel ◽  
Masaaki Umeda ◽  
Margret Sauter
Keyword(s):  
S Phase ◽  
Cyclin Dependent Kinase ◽  
Phase Progression

scholarly journals Activation of mammalian Chk1 during DNA replication arrest

2001 ◽  
Vol 154 (5) ◽  
pp. 913-924 ◽  
Author(s):  
Carmen Feijoo ◽  
Clare Hall-Jackson ◽  
Rong Wu ◽  
David Jenkins ◽  
Jane Leitch ◽  
...  
Keyword(s):  
Dna Replication ◽  
Mammalian Cells ◽  
S Phase ◽  
Global Pattern ◽  
Origin Firing ◽  
Replication Arrest ◽  
Molecule Inhibitor ◽  
Replication Block ◽  
Phase Progression ◽  
S Phase Checkpoint

Checkpoints maintain order and fidelity in the cell cycle by blocking late-occurring events when earlier events are improperly executed. Here we describe evidence for the participation of Chk1 in an intra-S phase checkpoint in mammalian cells. We show that both Chk1 and Chk2 are phosphorylated and activated in a caffeine-sensitive signaling pathway during S phase, but only in response to replication blocks, not during normal S phase progression. Replication block–induced activation of Chk1 and Chk2 occurs normally in ataxia telangiectasia (AT) cells, which are deficient in the S phase response to ionizing radiation (IR). Resumption of synthesis after removal of replication blocks correlates with the inactivation of Chk1 but not Chk2. Using a selective small molecule inhibitor, cells lacking Chk1 function show a progressive change in the global pattern of replication origin firing in the absence of any DNA replication. Thus, Chk1 is apparently necessary for an intra-S phase checkpoint, ensuring that activation of late replication origins is blocked and arrested replication fork integrity is maintained when DNA synthesis is inhibited.

Mechanisms regulating S phase progression in mammalian cells

10.2741/3523 ◽  
2009 ◽  
Vol Volume (14) ◽  
pp. 4199 ◽  
Author(s):  
Apolinar Maya-Mendoza
Keyword(s):  
Mammalian Cells ◽  
S Phase ◽  
Phase Progression

scholarly journals The Stress-activated Protein Kinase Hog1 Mediates S Phase Delay in Response to Osmostress

2009 ◽  
Vol 20 (15) ◽  
pp. 3572-3582 ◽  
Author(s):  
Gilad Yaakov ◽  
Alba Duch ◽  
María García-Rubio ◽  
Josep Clotet ◽  
Javier Jimenez ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
S Phase ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Replication Complex ◽  
Extracellular Stimuli ◽  
Phase Progression ◽  
Cell Cycle Machinery

Control of cell cycle progression by stress-activated protein kinases (SAPKs) is essential for cell adaptation to extracellular stimuli. Exposure of yeast to osmostress activates the Hog1 SAPK, which modulates cell cycle progression at G1 and G2 by the phosphorylation of elements of the cell cycle machinery, such as Sic1 and Hsl1, and by down-regulation of G1 and G2 cyclins. Here, we show that upon stress, Hog1 also modulates S phase progression. The control of S phase is independent of the S phase DNA damage checkpoint and of the previously characterized Hog1 cell cycle targets Sic1 and Hsl1. Hog1 uses at least two distinct mechanisms in its control over S phase progression. At early S phase, the SAPK prevents firing of replication origins by delaying the accumulation of the S phase cyclins Clb5 and Clb6. In addition, Hog1 prevents S phase progression when activated later in S phase or cells containing a genetic bypass for cyclin-dependent kinase activity. Hog1 interacts with components of the replication complex and delays phosphorylation of the Dpb2 subunit of the DNA polymerase. The two mechanisms of Hog1 action lead to delayed firing of origins and prolonged replication, respectively. The Hog1-dependent delay of replication could be important to allow Hog1 to induce gene expression before replication.

Inhibition of S-phase progression triggered by UVA-induced ROS does not require a functional DNA damage checkpoint response in mammalian cells

DNA Repair ◽  
2008 ◽  
Vol 7 (9) ◽  
pp. 1500-1516 ◽  
Author(s):  
Pierre-Marie Girard ◽  
Mariaelena Pozzebon ◽  
Fabien Delacôte ◽  
Thierry Douki ◽  
Violetta Smirnova ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mammalian Cells ◽  
S Phase ◽  
Dna Damage Checkpoint ◽  
Checkpoint Response ◽  
Phase Progression ◽  
Functional Dna

scholarly journals Regulation of p27 Degradation and S-Phase Progression by Ro52 RING Finger Protein

2006 ◽  
Vol 26 (16) ◽  
pp. 5994-6004 ◽  
Author(s):  
Abdelmajid Sabile ◽  
Andrea Michael Meyer ◽  
Christiane Wirbelauer ◽  
Daniel Hess ◽  
Ulrike Kogel ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Kinase Inhibitor ◽  
Ring Finger ◽  
E3 Ligase ◽  
S Phase ◽  
Dependent Manner ◽  
Ring Finger Protein ◽  
Catalytic Core ◽  
Finger Protein ◽  
Phase Progression

ABSTRACT Ubiquitin-mediated degradation of the cyclin-dependent kinase inhibitor p27 provides a powerful route for enforcing normal progression through the mammalian cell cycle. According to a current model, the ubiquitination of p27 during S-phase progression is mediated by SCFSkp2 E3 ligase that captures Thr187-phosphorylated p27 by means of the F-box protein Skp2, which in turn couples the bound substrate via Skp1 to a catalytic core complex composed of Cul1 and the Rbx/Roc RING finger protein. Here we identify Skp2 as a component of an Skp1-cullin-F-box complex that is based on a Cul1-Ro52 RING finger B-box coiled-coil motif family protein catalytic core. Ro52-containing complexes display E3 ligase activity and promote the ubiquitination of Thr187-phosphorylated p27 in a RING-dependent manner in vitro. The knockdown of Ro52 expression in human cells with small interfering RNAs causes the accumulation of p27 and the failure of cells to enter S phase. Importantly, these effects are abrogated by the simultaneous removal of p27. Taken together, these data suggest a key role for Ro52 RING finger protein in the regulation of p27 degradation and S-phase progression in mammalian cells and provide evidence for the existence of a Cul1-based catalytic core that utilizes Ro52 RING protein to promote ubiquitination.

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