Docosahexaenoic acid, a major constituent of fish oil diets, prevents activation of cyclin-dependent kinases and S-phase entry by serum stimulation in HT-29 cells

2001 ◽  
Vol 64 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Z.-Y. Chen ◽  
N.W. Istfan
Keyword(s):  
Docosahexaenoic Acid ◽  
Fish Oil ◽  
S Phase ◽  
Major Constituent ◽  
Cyclin Dependent Kinases ◽  
Serum Stimulation ◽  
Ht 29 ◽  
Phase Entry

scholarly journals Combined Inactivation of Pocket Proteins and APC/CCdh1 by Cdk4/6 Controls Recovery from DNA Damage in G1 Phase

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 550
Author(s):  
Indra A. Shaltiel ◽  
Alba Llopis ◽  
Melinda Aprelia ◽  
Rob Klompmaker ◽  
Apostolos Menegakis ◽  
...  
Keyword(s):  
Dna Damage ◽  
Normal Cell ◽  
S Phase ◽  
G1 Phase ◽  
Anaphase Promoting Complex ◽  
Inhibitory Effects ◽  
Pocket Proteins ◽  
Cyclin Dependent Kinases ◽  
Independent Functions ◽  
Phase Entry

Most Cyclin-dependent kinases (Cdks) are redundant for normal cell division. Here we tested whether these redundancies are maintained during cell cycle recovery after a DNA damage-induced arrest in G1. Using non-transformed RPE-1 cells, we find that while Cdk4 and Cdk6 act redundantly during normal S-phase entry, they both become essential for S-phase entry after DNA damage in G1. We show that this is due to a greater overall dependency for Cdk4/6 activity, rather than to independent functions of either kinase. In addition, we show that inactivation of pocket proteins is sufficient to overcome the inhibitory effects of complete Cdk4/6 inhibition in otherwise unperturbed cells, but that this cannot revert the effects of Cdk4/6 inhibition in DNA damaged cultures. Indeed, we could confirm that, in addition to inactivation of pocket proteins, Cdh1-dependent anaphase-promoting complex/cyclosome (APC/CCdh1) activity needs to be inhibited to promote S-phase entry in damaged cultures. Collectively, our data indicate that DNA damage in G1 creates a unique situation where high levels of Cdk4/6 activity are required to inactivate pocket proteins and APC/CCdh1 to promote the transition from G1 to S phase.

scholarly journals ERK Activity and G1 Phase Progression: Identifying Dispensable Versus Essential Activities and Primary Versus Secondary Targets

2007 ◽  
Vol 18 (4) ◽  
pp. 1457-1463 ◽  
Author(s):  
Jessie Villanueva ◽  
Yuval Yung ◽  
Janice L. Walker ◽  
Richard K. Assoian
Keyword(s):  
Cyclin D1 ◽  
Map Kinases ◽  
S Phase ◽  
G1 Phase ◽  
Cyclin Dependent Kinases ◽  
Mechanistic Analysis ◽  
Phase Progression ◽  
Erk Activity ◽  
Phase Entry ◽  
Stimulation Of

The ERK subfamily of MAP kinases is a critical regulator of S phase entry. ERK activity regulates the induction of cyclin D1, and a sustained ERK signal is thought to be required for this effect, at least in fibroblasts. We now show that early G1 phase ERK activity is dispensable for the induction of cyclin D1 and that the critical ERK signaling period is restricted to 3–6 h after mitogenic stimulation of quiescent fibroblasts. Similarly, early G1 phase ERK activity is dispensable for entry into S phase. Moreover, if cyclin D1 is expressed ectopically, ERK activity becomes dispensable throughout the G1 phase. In addition to its effect on cyclin D1, ERK activity is thought to contribute to the down-regulation of p27kip1. We found that this effect is restricted to late G1/S phase. Mechanistic analysis showed that the ERK effect on p27kip1 is mediated by Skp2 and is secondary to its effect on cyclin D1. Our results emphasize the importance of mid-G1 phase ERK activity and resolve primary versus secondary ERK targets within the G1 phase cyclin-dependent kinases.

scholarly journals E2F-Dependent Histone Acetylation and Recruitment of the Tip60 Acetyltransferase Complex to Chromatin in Late G1

2004 ◽  
Vol 24 (10) ◽  
pp. 4546-4556 ◽  
Author(s):  
Stefan Taubert ◽  
Chiara Gorrini ◽  
Scott R. Frank ◽  
Tiziana Parisi ◽  
Miriam Fuchs ◽  
...  
Keyword(s):  
Gene Activation ◽  
S Phase ◽  
Dominant Negative ◽  
Direct Role ◽  
Serum Stimulation ◽  
Ectopic Activation ◽  
H3 Acetylation ◽  
Target Promoters ◽  
Phase Entry

ABSTRACT E2F proteins can either activate or repress transcription. Following mitogenic stimulation, repressive E2F4-p130-histone deacetylase complexes dissociate from, while activating species (E2F1, -2, and -3) associate with, target promoters. Histones H3 and H4 simultaneously become hyperacetylated, but it remains unclear whether this is a prerequisite or a consequence of E2F binding. Here, we show that activating E2F species are required for hyperacetylation of target chromatin in human cells. Overexpression of a dominant-negative (DN) E2F1 mutant in serum-stimulated T98G cells blocked all E2F binding, H4 acetylation, and, albeit partially, H3 acetylation. Target gene activation and S-phase entry were also blocked by DN E2F1. Conversely, ectopic activation of E2F1 rapidly induced H3 and H4 acetylation, demonstrating a direct role for E2F in these events. E2F1 was previously shown to bind the histone acetyltransferases (HATs) p300/CBP and PCAF/GCN5. In our hands, ectopically expressed E2F1 also bound the unrelated HAT Tip60 and induced recruitment of five subunits of the Tip60 complex (Tip60, TRRAP, p400, Tip48, and Tip49) to target promoters in vivo. Moreover, E2F-dependent recruitment of Tip60 to chromatin occurred in late G1 following serum stimulation. We speculate that the activities of multiple HAT complexes account for E2F-dependent acetylation, transcription, and S-phase entry.

scholarly journals A Skp2 autoinduction loop and restriction point control

2007 ◽  
Vol 178 (5) ◽  
pp. 741-747 ◽  
Author(s):  
Yuval Yung ◽  
Janice L. Walker ◽  
James M. Roberts ◽  
Richard K. Assoian
Keyword(s):  
S Phase ◽  
Cyclin Dependent Kinase ◽  
Embryonic Fibroblasts ◽  
Papilloma Virus ◽  
Restriction Point ◽  
Pocket Proteins ◽  
Serum Stimulation ◽  
Point Control ◽  
Phase Progression ◽  
Phase Entry

We describe a self-amplifying feedback loop that autoinduces Skp2 during G1 phase progression. This loop, which contains Skp2 itself, p27kip1 (p27), cyclin E–cyclin dependent kinase 2, and the retinoblastoma protein, is closed through a newly identified, conserved E2F site in the Skp2 promoter. Interference with the loop, by knockin of a Skp2-resistant p27 mutant (p27T187A), delays passage through the restriction point but does not interfere with S phase entry under continuous serum stimulation. Skp2 knock down inhibits S phase entry in nontransformed mouse embryonic fibroblasts but not in human papilloma virus–E7 expressing fibroblasts. We propose that the essential role for Skp2-dependent degradation of p27 is in the formation of an autoinduction loop that selectively controls the transition to mitogen-independence, and that Skp2-dependent proteolysis may be dispensable when pocket proteins are constitutively inactivated.

scholarly journals Docosahexaenoic acid accumulates in cardiolipin and enhances HT-29 cell oxidant production

1998 ◽  
Vol 39 (8) ◽  
pp. 1583-1588 ◽  
Author(s):  
Steven M. Watkins ◽  
Lynne C. Carter ◽  
J. Bruce German
Keyword(s):  
Docosahexaenoic Acid ◽  
Oxidant Production ◽  
Ht 29
Sign in / Sign up

Export Citation Format

Share Document