ABSTRACT
Eukaryotic translation initiation factor 6 (eIF6) affects the maturation of 60S ribosomal subunits. Found in yeast and mammalian cells, eIF6 is primarily located in the cytoplasm of mammalian cells. Emerging evidence has demonstrated that the dysregulated expression of eIF6 is important in several types of human cancer, including head and neck carcinoma, colorectal cancer, non-small cell lung cancer and ovarian serous adenocarcinoma. However, the molecular mechanisms by which eIF6 functions during tumor formation and progression remain elusive. The present review focuses on recent progress in terms of the mechanisms and functions of eIF6 in human tumorigenesis or cancer cell lines, along with the signal transduction pathways in which this novel translation initiation factor may participate. Oncogenic Ras activates Notch-1 and promotes transcription of eIF6 via a recombining binding protein suppressor of Hairless-dependent mechanism. In addition, overexpression of eIF6 results in aberrant activation of the Wnt/ß-catenin signaling pathway. Similarly, overexpressed eIF6 regulates its downstream modulator, cell division control protein 42, which in turn affects oncogenesis. Finally, the potential of eIF6 as a biomarker for diagnosis of cancer is also discussed in the present review.
ABSTRACT
Two isoreticular metal-organic frameworks with chemical formulae [Cu(L)(4,4'-bipy)(H2O)]n 1.5nCH3CN (1) and [Cu(L)(4,4'-bipy)(H2O)]n·4nH2O (2) (H2L = diphenylmethane-4,4'-dicarboxylic acid) were synthesized and structurally characterized. They show the CdSO4 (6(5) 8) net and have an obvious 1D channel that is spread along the crystallographic c axis. More importantly, 1 shows high selectivity for H2 over N2 and CO2 at low pressure, which could be confirmed via computational calculations using the Connolly algorithm to reveal the size and shape of accessible voids. The incorporation of the drug 5-fluorouracil (5-FU) into the desolvated 1 was around 27.5 wt% per gram of the dehydrated 1. 5-FU is released in a highly controlled and progressive fashion with 61% of the drug released after 95 hours. In addition, we have applied molecular docking calculations to investigate the preferred conformation of 5-FU molecules upon binding to MOF 1. These calculations provide a structural basis to explain the 5-FU release from MOF 1.
