CPI-17 drives oncogenic Ras signaling in human melanomas via Ezrin-Radixin-Moesin family proteins

Hyperactive Ras signaling has strong oncogenic effects causing several different forms of cancer. Hyperactivity is frequently induced by mutations within Ras itself, which account for up to 30% of all human cancers. In addition, hyperactive Ras signaling can also be triggered independent of Ras by either mutation or by misexpression of various upstream regulators and immediate downstream effectors. We have previously reported that C-kinase potentiated protein phosphatase-1 inhibitor of 17 kDa (CPI-17) can drive Ras activity and promote tumorigenic transformation by inhibition of the tumor suppressor Merlin. We now describe an additional element of this oncogenic mechanism in the form of the ezrin-radixin-moesin (ERM) protein family, which exhibits opposing roles in Ras activity control. Thus, CPI-17 drives Ras activity and tumorigenesis in a two-fold way; inactivation of the tumor suppressor merlin and activation of the growth promoting ERM family. The in vivo significance of this oncogenic switch is highlighted by demonstrating CPI-17’s involvement in human melanoma pathogenesis

Small-scale structure of the galactic cirrus emission

We examined the Fourier power spectrum characteristics of cirrus structures in 13 sky fields with faint to bright cirrus emission observed with ISOPHOT in the 90--200µm wavelength range in order to study variations of the spectral index $\alpha$. We found that $\alpha$ varies from field to field with --5.3 $\le$ $\alpha$ $\le$ --2.1. It depends on the absolute surface brightness and on the hydrogen column density. We also found different spectral indices for the same sky region at different wavelengths. Longer wavelength measurements show steeper power spectra. This can be explained by the presence of dust at various temperatures, in particular of a cold extended component. For the faintest areas of the far-infrared sky we derive a wavelength independent spectral index of $\alpha$ = --2.3$\pm$0.6 for the cirrus power spectrum. The application of the correct spectral index is a precondition for the proper disentanglement of the cirrus foreground component of the Cosmic Far-Infrared Background and its fluctuations.Comment: 10 pages; 7 figures; Astronomy & Astrophysics, accepte

Dust emission from 3C radio galaxies and quasars: New ISO observations favour the unified scheme

In order to test the unified scheme for luminous radio galaxies and quasars we observed 10 galaxy/quasar pairs from the 3CR catalogue with ISOPHOT at infrared wavelengths between 5 and 180 micron. Each pair was selected such that both the 178 MHz luminosity and the redshift match as close as possible between the radio galaxy and the quasar in order to minimize effects of cosmic evolution. 13 of the 20 sources were detected in at least one waveband. 12 sources show clear evidence of a thermal bump at FIR wavelength, while in the remaining 7 sources the upper limits are still compatible with the presence of luminous dust emission. In agreement with the predictions of the unified scheme, the quasars and galaxies in our sample cannot be distinguished by their observed mid- and far-infrared properties. This is in contrast to the IRAS results which indicated that radio galaxies radiate significantly less mid- to far-infrared emission than quasars. However, the IRAS samples are dominated by low-redshift sources (z < 0.5), while our sample contains several of the most luminous radio galaxies at redshift z ~ 1. The latter have already been suspected to contain a hidden quasar for other reasons, e.g. an extended emission line region aligned with the radio axis. From the ratio between FIR luminosity emitted by dust and the radio power at 178 MHz, we conclude that the radio galaxy/quasar unification might be perfectly valid for the most luminous 3C sources at high redshift (z > 0.8). At lower redshifts (z < 0.5), however, some of the FRII radio galaxies contain active nuclei which emit less UV-optical continuum than the quasars of similar radio power. (abrigded)Comment: 10 pages, 6 figures, Late

TcOPT3, a Member of Oligopeptide Transporters from the Hyperaccumulator Thlaspi caerulescens, Is a Novel Fe/Zn/Cd/Cu Transporter

BACKGROUND: Thlaspi caerulescens is a natural selected heavy metal hyperaccumulator that can not only tolerate but also accumulate extremely high levels of heavy metals in the shoots. Thus, to identify the transportors involved in metal long-distance transportation is very important for understanding the mechanism of heavy metal accumulation in this hyperaccumulator. METHODOLOGY/PRINCIPAL FINDINGS: We cloned and characterized a novel gene TcOPT3 of OPT family from T. caerulescens. TcOPT3 was pronouncedly expressed in aerial parts, including stem and leaf. Moreover, in situ hybridization analyses showed that TcOPT3 expressed in the plant vascular systems, especially in the pericycle cells that may be involved in the long-distance transportation. The expression of TcOPT3 was highly induced by iron (Fe) and zinc (Zn) deficiency, especially in the stem and leaf. Sub-cellular localization showed that TcOPT3 was a plasma membrane-localized protein. Furthermore, heterogonous expression of TcOPT3 by mutant yeast (Saccharomyces cerevisiae) complementation experiments demonstrated that TcOPT3 could transport Fe(2+) and Zn(2+). Moreover, expression of TcOPT3 in yeast increased metal (Fe, Zn, Cu and Cd) accumulation and resulted in an increased sensitivity to cadmium (Cd) and copper (Cu). CONCLUSIONS: Our data demonstrated that TcOPT3 might encode an Fe/Zn/Cd/Cu influx transporter with broad-substrate. This is the first report showing that TcOPT3 may be involved in metal long-distance transportation and contribute to the heavy metal hyperaccumulation