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91.
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Andrey Poleshko Andrew V Kossenkov Natalia Shalginskikh Anna Pecherskaya Anna Pecherskaya Margret B Einarson Margret B Einarson Anna Marie Skalka Anna Marie Skalka Richard A Katz Richard A Katz 《Epigenetics》2014,9(9):1280-1289
Cellular identity in both normal and disease processes is determined by programmed epigenetic activation or silencing of specific gene subsets. Here, we have used human cells harboring epigenetically silent GFP-reporter genes to perform a genome-wide siRNA knockdown screen for the identification of cellular factors that are required to maintain epigenetic gene silencing. This unbiased screen interrogated 21,121 genes, and we identified and validated a set of 128 protein factors. This set showed enrichment for functional categories, and protein-protein interactions. Among this set were known epigenetic silencing factors, factors with no previously identified role in epigenetic gene silencing, as well as unstudied factors. The set included non-nuclear factors, for example, components of the integrin-adhesome. A key finding was that the E1 and E2 enzymes of the small ubiquitin-like modifier (SUMO) pathway (SAE1, SAE2/UBA2, UBC9/UBE2I) are essential for maintenance of epigenetic silencing. This work provides the first genome-wide functional view of human factors that mediate epigenetic gene silencing. The screen output identifies novel epigenetic factors, networks, and mechanisms, and provides a set of candidate targets for epigenetic therapy and cellular reprogramming. 相似文献
93.
Pavel N. Shashkin Laura C. Huang Joseph Larner George E. Vandenhoff Abram Katz 《Experimental diabetes research》2002,3(3):163-169
Two classes of inositol phosphoglycans have been implicated as
second messengers of insulin, one that activates pyruvate dehydrogenase
and contains D-chiroinositol, and one that inhibits cyclic
AMP–dependent protein kinase and contains myoinositol. We examined
the effects of a 3-day fast on muscle contents of inositols
in healthy humans. An oral glucose tolerance test was performed
and a biopsy was obtained from the quadriceps femoris muscle
after an overnight fast and after a 72-hour fast. The 72-hour fast
significantly increased plasma glucose (1.5- to 2-fold) and insulin
(2- to 4-fold) after glucose ingestion versus the values after the
overnight fast, indicating the manifestation of peripheral insulin
resistance. The 72-hour fast resulted in an ∼20% decrease in the
muscle content of D-chiroinositol (P < 0.02), but no change in the
myoinositol content. These data demonstrate that fasting specifically
decreases the muscle content of D-chiroinositol in human muscle
and this may contribute to the finding that insulin-mediated activation
of pyruvate dehydrogenase is attenuated after short-term
starvation. 相似文献
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Adriana Katz Daniel M. Tal Dan Heller Haim Haviv Bilal Rabah Yaniv Barkana Arie L. Marcovich Steven J. D. Karlish 《The Journal of biological chemistry》2014,289(30):21153-21162
In the ciliary epithelium of the eye, the pigmented cells express the α1β1 isoform of Na,K-ATPase, whereas the non-pigmented cells express mainly the α2β3 isoform of Na,K-ATPase. In principle, a Na,K-ATPase inhibitor with selectivity for α2 could effectively reduce intraocular pressure with only minimal local and systemic toxicity. Such an inhibitor could be applied topically provided it was sufficiently permeable via the cornea. Previous experiments with recombinant human α1β1, α2β1, and α3β1 isoforms showed that the classical cardiac glycoside, digoxin, is partially α2-selective and also that the trisdigitoxose moiety is responsible for isoform selectivity. This led to a prediction that modification of the third digitoxose might increase α2 selectivity. A series of perhydro-1,4-oxazepine derivatives of digoxin have been synthesized by periodate oxidation and reductive amination using a variety of R-NH2 substituents. Several derivatives show enhanced selectivity for α2 over α1, close to 8-fold in the best case. Effects of topically applied cardiac glycosides on intraocular pressure in rabbits have been assessed by their ability to either prevent or reverse acute intraocular pressure increases induced by 4-aminopyridine or a selective agonist of the A3 adenosine receptor. Two relatively α2-selective digoxin derivatives efficiently normalize the ocular hypertension, by comparison with digoxin, digoxigenin, or ouabain. This observation is consistent with a major role of α2 in aqueous humor production and suggests that, potentially, α2-selective digoxin derivatives could be of interest as novel drugs for control of intraocular pressure. 相似文献
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The protein tyrosine kinase pp125FAK (focal adhesion kinase, or FAK) is expressed by a variety of cell types and has been implicated in integrin-mediated signaling events. We explored the potential functions of FAK by expressing it de novo in a cell type lacking FAK. We showed previously that cultured human macrophages lack FAK yet still have well-formed focal contacts. Adenovirus-mediated expression of FAK results in the appearance of FAK protein, which localizes to focal contacts and becomes tyrosine-phosphorylated without perturbing overall cell morphology or focal contacts. FAK associates with CSK 48 h after infection and recruits it to focal contacts. Tyrosine phosphorylation of p130cas but not of paxillin is stimulated after FAK expression. The phosphorylation of p130cas is lost at 48 h in parallel with CSK accumulation in focal contacts. The ERK2 form of MAP kinase is similarly activated at 12-24 h, but it also returns to low levels at 48 h. These findings demonstrate that FAK can be reconstituted to focal contacts in cells that lack it without affecting cell morphology or focal contact structure. FAK can regulate the distribution and activities of elements of the MAP kinase signaling pathway. 相似文献
100.
Photosynthetic inorganic carbon utilization and growth of Porphyra linearis (Rhodophyta) 总被引:2,自引:0,他引:2
Alvaro Israel Shlomit Katz Zvy Dubinsky John E. Merrill Michael Friedlander 《Journal of applied phycology》1999,11(5):447-453
Photosynthetic (oxygen evolution) and growth (biomass increase) responses to ambient pH and inorganic carbon (Ci) supply were
determined for Porphyralinearis grown in 0.5 L glass cylinders in the laboratory, or in 40 L fibreglass outdoor tanks with running seawater. While net photosynthetic
rates were uniform at pH 6.0–8.0, dropping only at pH 8.7, growth rates were significantly affected by pH levels other than
that of seawater (c. pH 8.3). In glass cylinders, weekly growth rates averaged 76% at external pH 8.0, 13% at pH 8.7 and 26%
at pH 7.0. Photosynthetic O2 evolution on a daily basis(i.e. total O2 evolved during day time less total O2 consumed during night time) was similar to the growth responses at all experimental pH levels, apparently due to high dark
respiration rates measured at acidic pH. Weekly growth rates averaged 53% in algae grown in fibreglass tanks aerated with
regular air (360 mg L-1 CO2) and 28% in algae grown in tanks aerated with CO2-enriched air (750 mg L-1 CO2). The pH of the seawater medium in which P. linear is was grown increased slightly during the day and only rarely reached 9.0. The pH at the boundary layer of algae submerged
in seawater increased in response to light reaching, about pH 8.9 within minutes, or remained unchanged for algae submerged
in a CO2-free artificial sea water medium. Photosynthesis of P. linearissaturated at Ci concentrations of seawater (K0.5560 μM at pH 8.2) and showed low photosynthetic affinity for CO2(K0.5 61 μM) at pH 6.0. It is therefore concluded that P. linearisuses primarily CO2 with HCO3
- being an alternative source of Ci for photosynthesis. Its fast growth could be related to the enzyme carbonic anhydrase whose
activity was detected intra- and extracellularly.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献