scholarly journals Hydrogen Peroxide CausesRAD9-dependent Cell Cycle Arrest in G2inSaccharomyces cerevisiaewhereas Menadione Causes G1Arrest Independent ofRAD9Function

1998 ◽  
Vol 273 (15) ◽  
pp. 8564-8571 ◽  
Author(s):  
Jacinta A. Flattery-O’Brien ◽  
Ian W. Dawes
Keyword(s):  
Cell Cycle ◽  
Hydrogen Peroxide ◽  
Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Dependent Cell

scholarly journals Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery

2006 ◽  
Vol 175 (5) ◽  
pp. 779-789 ◽  
Author(s):  
Timothy J. Phalen ◽  
Kelly Weirather ◽  
Paula B. Deming ◽  
Vikas Anathy ◽  
Alan K. Howe ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hydrogen Peroxide ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Ectopic Expression ◽  
Structural Transitions ◽  
Mitogenic Signaling ◽  
Cycle Arrest ◽  
Subcellular Processes ◽  
Dependent Cell

Inactivation of eukaryotic 2-Cys peroxiredoxins (Prxs) by hyperoxidation has been proposed to promote accumulation of hydrogen peroxide (H2O2) for redox-dependent signaling events. We examined the oxidation and oligomeric states of PrxI and -II in epithelial cells during mitogenic signaling and in response to fluxes of H2O2. During normal mitogenic signaling, hyperoxidation of PrxI and -II was not detected. In contrast, H2O2-dependent cell cycle arrest was correlated with hyperoxidation of PrxII, which resulted in quantitative recruitment of ∼66- and ∼140-kD PrxII complexes into large filamentous oligomers. Expression of cyclin D1 and cell proliferation did not resume until PrxII-SO2H was reduced and native PrxII complexes were regenerated. Ectopic expression of PrxI or -II increased Prx-SO2H levels in response to oxidant exposure and failed to protect cells from arrest. We propose a model in which Prxs function as peroxide dosimeters in subcellular processes that involve redox cycling, with hyperoxidation controlling structural transitions that alert cells of perturbations in peroxide homeostasis.

scholarly journals MdmX Protects p53 from Mdm2-Mediated Degradation

2000 ◽  
Vol 20 (3) ◽  
pp. 1001-1007 ◽  
Author(s):  
Mark W. Jackson ◽  
Steven J. Berberich
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Nuclear Export ◽  
P53 Protein ◽  
Ring Finger ◽  
Ring Finger Domain ◽  
Cycle Arrest ◽  
Dependent Cell ◽  
Potential Basis ◽  
P53 Tumor Suppressor Protein

ABSTRACT The p53 tumor suppressor protein is stabilized in response to cellular stress, resulting in activation of genes responsible for either cell cycle arrest or apoptosis. The cellular pathway for releasing normal cells from p53-dependent cell cycle arrest involves the Mdm2 protein. Recently, a p53-binding protein with homology to Mdm2 was identified and called MdmX. Like Mdm2, MdmX is able to bind p53 and inhibit p53 transactivation; however, the ability of MdmX to degrade p53 has yet to be examined. We report here that MdmX is capable of associating with p53 yet is unable to facilitate nuclear export or induce p53 degradation. In addition, expression of MdmX can reverse Mdm2-targeted degradation of p53 while maintaining suppression of p53 transactivation. Using a series of MdmX deletions, we have determined that there are two distinct domains of the MdmX protein that can stabilize p53 in the presence of Mdm2. One domain requires MdmX interaction with p53 and results in the retention of both proteins within the nucleus and repression of p53 transactivation. The second domain involves the MdmX ring finger and results in stabilization of p53 and an increase in p53 transactivation. The potential basis for stabilization and increased p53 transactivation by the MdmX ring finger domain is discussed. Based on these observations, we propose that the MdmX protein may function to maintain a nuclear pool of p53 protein in undamaged cells.

scholarly journals Enforced Expression of p14ARF Induces p53-Dependent Cell Cycle Arrest but Not Apoptosis

Cell Cycle ◽  
2005 ◽  
Vol 4 (3) ◽  
pp. 465-472 ◽  
Author(s):  
Stuart Gallagher ◽  
Richard F. Kefford ◽  
Helen Rizos
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Dependent Cell

scholarly journals Aberrant Expression of Nucleostemin Activates p53 and Induces Cell Cycle Arrest via Inhibition of MDM2

2008 ◽  
Vol 28 (13) ◽  
pp. 4365-4376 ◽  
Author(s):  
Mu-Shui Dai ◽  
Xiao-Xin Sun ◽  
Hua Lu
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Ribosomal Proteins ◽  
Cell Cycle Checkpoint ◽  
Aberrant Expression ◽  
Cycle Arrest ◽  
Reduce Cell Proliferation ◽  
Cycle Checkpoint ◽  
Dependent Cell

ABSTRACT The nucleolar protein nucleostemin (NS) is essential for cell proliferation and early embryogenesis. Both depletion and overexpression of NS reduce cell proliferation. However, the mechanisms underlying this regulation are still unclear. Here, we show that NS regulates p53 activity through the inhibition of MDM2. NS binds to the central acidic domain of MDM2 and inhibits MDM2-mediated p53 ubiquitylation and degradation. Consequently, ectopic overexpression of NS activates p53, induces G1 cell cycle arrest, and inhibits cell proliferation. Interestingly, the knockdown of NS by small interfering RNA also activates p53 and induces G1 arrest. These effects require the ribosomal proteins L5 and L11, since the depletion of NS enhanced their interactions with MDM2 and the knockdown of L5 or L11 abrogated the NS depletion-induced p53 activation and cell cycle arrest. These results suggest that a p53-dependent cell cycle checkpoint monitors changes of cellular NS levels via the impediment of MDM2 function.

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