Cyclins

Publication Title: 
Experimental Cell Research

Cellular senescence is a state of irreversible cell cycle arrest in which normal cells at the end of their lifespan fail to enter into DNA synthesis upon serum or growth factor stimulation. We examined whether proteins required for G1/S cell cycle progression were irreversibly down-regulated in senescent human fibroblasts. Both the 44- and 42-kDa forms of the MAP-kinase protein were expressed at similar levels in young and senescent cells.

Author(s): 
Afshari, C. A.
Vojta, P. J.
Annab, L. A.
Futreal, P. A.
Willard, T. B.
Barrett, J. C.
Publication Title: 
The EMBO journal

Telomere loss has been proposed as a mechanism for counting cell divisions during aging in normal somatic cells. How such a mitotic clock initiates the intracellular signalling events that culminate in G1 cell cycle arrest and senescence to restrict the lifespan of normal human cells is not known. We investigated the possibility that critically short telomere length activates a DNA damage response pathway involving p53 and p21(WAF1) in aging cells.

Author(s): 
Vaziri, H.
West, M. D.
Allsopp, R. C.
Davison, T. S.
Wu, Y. S.
Arrowsmith, C. H.
Poirier, G. G.
Benchimol, S.
Publication Title: 
Oncogene

Replicative senescence is thought to be a significant barrier to human tumorigenesis, which in human fibroblasts, and many other cell types, can be overcome experimentally by combined loss of function of p53 and Rb 'pathways'. To avoid the confounding pleiotropic effects of HPVE7 frequently used in such studies, here we have employed retroviral vectors over-expressing CDK4 or CDK6 as a more representative model of naturally-occurring mutations targeting the Rb pathway.

Author(s): 
Morris, Mark
Hepburn, Peter
Wynford-Thomas, David
Publication Title: 
Experimental Cell Research

Numerous studies have shown that supplementation of the growth medium of human fibroblasts with dexamethasone at physiologic concentrations extends replicative lifespan up to 30%. While this extension of lifespan has been used to probe various aspects of the senescent phenotype, no mechanism for the increased lifespan of human fibroblasts grown in the presence of dexamethasone has ever been identified.

Author(s): 
Mawal-Dewan, Madhu
Frisoni, Lorenza
Cristofalo, Vincent J.
Sell, Christian
Publication Title: 
EMBO reports

Current models envision replicative senescence to be under dual control by the p53 and retinoblastoma (RB) tumour-suppressor pathways. The role of the p16(INK4a)-RB pathway is controversial, and the function of RB in human cells has not been tested directly. We used targeted homologous recombination to knock out one copy of RB in presenescent human fibroblasts. During entry into senescence, RB+/- cells underwent spontaneous loss of heterozygosity and the resultant RB-/- clones bypassed senescence. The extended lifespan phase was eventually terminated by a crisis-like state.

Author(s): 
Wei, Wenyi
Herbig, Utz
Wei, Shan
Dutriaux, Annie
Sedivy, John M.
Publication Title: 
PloS One

The chronological lifespan of eukaryotic organisms is extended by the mutational inactivation of conserved growth-signaling pathways that regulate progression into and through the cell cycle. Here we show that in the budding yeast S. cerevisiae, these and other lifespan-extending conditions, including caloric restriction and osmotic stress, increase the efficiency with which nutrient-depleted cells establish or maintain a cell cycle arrest in G1.

Author(s): 
Weinberger, Martin
Feng, Li
Paul, Anita
Smith, Daniel L.
Hontz, Robert D.
Smith, Jeffrey S.
Vujcic, Marija
Singh, Keshav K.
Huberman, Joel A.
Burhans, William C.
Publication Title: 
The Journal of Biological Chemistry

Inhibition of the up-regulated telomerase activity in cancer cells has previously been shown to slow cell growth but only after prior telomere shortening. Previously, we have reported that, unexpectedly, a hairpin short interfering RNA specifically targeting human telomerase RNA rapidly inhibits the growth of human cancer cells independently of p53 or telomere length and without bulk telomere shortening (Li, S., Rosenberg, J. E., Donjacour, A. A., Botchkina, I. L., Hom, Y. K., Cunha, G. R., and Blackburn, E. H. (2004) Cancer Res. 64, 4833-4840).

Author(s): 
Li, Shang
Crothers, Julia
Haqq, Christopher M.
Blackburn, Elizabeth H.
Publication Title: 
Anticancer Research

BACKGROUND: Former studies have shown that extract from American ginseng (Panax quinquefolius) may possess certain antiproliferative effects on cancer cells. In this study, the chemical constituents of both untreated and heat-processed American ginseng and their antiproliferative activities on human breast cancer cells were evaluated. MATERIALS AND METHODS: American ginseng roots were steamed at 120 degrees C for 1 h or 2 h. The major ginsenosides in the two steamed and in the unsteamed extracts were quantitatively determined using high performance liquid chromatography (HPLC).

Author(s): 
Wang, Chong-Zhi
Aung, Han H.
Zhang, Bin
Sun, Shi
Li, Xiao-Li
He, Hui
Xie, Jing-Tian
He, Tong-Chuan
Du, Wei
Yuan, Chun-Su
Publication Title: 
The Journal of Nutrition

Piceatannol, a naturally occurring analog of resveratrol, was previously identified as the active ingredient in herbal preparations in folk medicine and as an inhibitor of p72(Syk). We studied the effects of piceatannol on growth, proliferation, differentiation and cell cycle distribution profile of the human colon carcinoma cell line Caco-2. Growth of Caco-2 and HCT-116 cells was analyzed by crystal violet assay, which demonstrated dose- and time-dependent decreases in cell numbers. Treatment of Caco-2 cells with piceatannol reduced proliferation rate.

Author(s): 
Wolter, Freya
Clausnitzer, Antje
Akoglu, Bora
Stein, Jürgen
Publication Title: 
PloS One

The chronological lifespan of eukaryotic organisms is extended by the mutational inactivation of conserved growth-signaling pathways that regulate progression into and through the cell cycle. Here we show that in the budding yeast S. cerevisiae, these and other lifespan-extending conditions, including caloric restriction and osmotic stress, increase the efficiency with which nutrient-depleted cells establish or maintain a cell cycle arrest in G1.

Author(s): 
Weinberger, Martin
Feng, Li
Paul, Anita
Smith, Daniel L.
Hontz, Robert D.
Smith, Jeffrey S.
Vujcic, Marija
Singh, Keshav K.
Huberman, Joel A.
Burhans, William C.

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