Cellular senescence limits the replicative capacity of normal cells and acts as an intrinsic barrier that protects against the development of cancer. Telomere shortening-induced replicative senescence is dependent on the ATM-p53-p21 pathway but additional genes likely contribute to senescence. Here, we show that the p53-responsive gene BTG2 plays an essential role in replicative senescence. Similar to p53 and p21 depletion, BTG2 depletion in human fibroblasts leads to an extension of cellular lifespan, and ectopic BTG2 induces senescence independently of p53.
Proceedings of the National Academy of Sciences of the United States of America
The canonical function of the human telomerase protein (hTERT) is to synthesize telomeric DNA, but it has other biological activities, including enhancing cell proliferation, decreasing apoptosis, regulating DNA damage responses, and increasing cellular proliferative lifespan. The mechanistic relationships among these activities are not understood. We previously demonstrated that ectopic hTERT expression in primary human mammary epithelial cells diminishes their requirement for exogenous mitogens, thus giving them a proliferative advantage in a mitogen-depleted environment.
BACKGROUND AND PURPOSE: Artemisinin and its derivatives exhibit potent immunosuppressive activity. The purpose of the current study was to examine the immunosuppressive activity of artemether directly on T lymphocytes and to explore its potential mode of action. EXPERIMENTAL APPROACH: In vitro, T-cell proliferation was measured using [(3)H]-thymidine incorporation assay in cells stimulated with ConA, alloantigen and anti-CD3 antibody. CFSE-labeled cell division and cell cycle distribution were monitored by flow cytometry.
Glycine N-methyltransferase (GNMT) catabolizes S-adenosylmethionine (SAMe), the main methyl donor of the body. Patients with cirrhosis show attenuated GNMT expression, which is absent in hepatocellular carcinoma (HCC) samples. GNMT(-/-) mice develop spontaneous steatosis that progresses to steatohepatitis, cirrhosis, and HCC. The liver is highly enriched with innate immune cells and plays a key role in the body's host defense and in the regulation of inflammation. Chronic inflammation is the major hallmark of nonalcoholic steatohepatitis (NASH) progression.
Fibroblast growth factors are key proteins in many intercellular signaling networks. They normally remain attached to the extracellular matrix, which confers on them a considerable stability. The unrestrained accumulation of fibroblast growth factors in the extracellular milieu, either due to uncontrolled synthesis or enzymatic release, contributes to the pathology of many diseases. Consequently, the neutralization of improperly mobilized fibroblast growth factors is of clear therapeutic interest.
Basic fibroblast growth factor (bFGF)-like immunoreactivity was detected in extracts of Panax ginseng root by using a sensitive two-site enzyme immunoassay specific for human bFGF (hbFGF). In an investigation of the molecular properties of this bFGF-like molecule (bFGF-LI), the bFGF-LI and hbFGF were found to be equivalent with respect to antigenicity, molecular weight, isoelectric point, affinity for binding to heparin, and mitogenic activity toward BALB/c3T3 fibroblasts.