µ-Calpain Conversion of Antiapoptotic Bfl-1 (BCL2A1) into a Prodeath Factor Reveals Two Distinct alpha-Helices Inducing Mitochondria-Mediated Apoptosis

Anti-apoptotic Bfl-1 and pro-apoptotic Bax, two members of the Bcl-2 family sharing a similar structural fold, are classically viewed as antagonist regulators of apoptosis. However, both proteins were reported to be death inducers following cleavage by the cysteine protease µ-calpain. Here we demonstrate that calpain-mediated cleavage of full-length Bfl-1 induces the release of C-terminal membrane active α-helices that are responsible for its conversion into a pro-apoptotic factor. A careful comparison of the different membrane-active regions present in the Bfl-1 truncated fragments with homologous domains of Bax show that helix α5, but not α6, of Bfl-1 induces cell death and cytochrome c release from purified mitochondria through a Bax/Bak-dependent mechanism. In contrast, both helices α5 and α6 of Bax permeabilize mitochondria regardless of the presence of Bax or Bak. Moreover, we provide evidence that the α9 helix of Bfl-1 promotes cytochrome c release and apoptosis through a unique membrane-destabilizing action whereas Bax-α9 does not display such activities. Hence, despite a common 3D-structure, C-terminal toxic domains present on Bfl-1 and Bax function in a dissimilar manner to permeabilize mitochondria and induce apoptosis. These findings provide insights for designing therapeutic approaches that could exploit the cleavage of endogenous Bcl-2 family proteins or the use of Bfl-1/Bax-derived peptides to promote tumor cell clearance

IL-1β induces eotaxin gene transcription in A549 airway epithelial cells through NF-κB

Eotaxin is an asthma-related C-C chemokine that is produced in response to interleukin-1beta (IL-1beta). We detected an increase in newly transcribed eotaxin mRNA in IL-1beta-stimulated airway epithelial cells. Transient transfection assays using promoter-reporter constructs identified a region as essential for IL-1beta-induced increases in eotaxin transcription. Using site-directed mutagenesis, we found that a nuclear factor-kappaB (NF-kappaB) site located 46 bp upstream from the transcriptional start site was both necessary and sufficient for IL-1beta induction of reporter construct activity. Electrophoretic mobility shift assay demonstrated that IL-1beta-stimulated airway epithelial cells produced p50 and p65 protein that bound this site in a sequence-specific manner. The functional importance of the NF-kappaB site was demonstrated by coexpression experiments in which increasing doses of p65 expression vector were directly associated with reporter activity exclusively in constructs with an intact NF-kappaB site (r(2) = 0.97, P = 0.002). Moreover, IL-1beta-induced increases in eotaxin mRNA expression are inhibited by inhibitors of NF-kappaB. Our findings implicate NF-kappaB and its binding sequence in IL-1beta-induced transcriptional activation of the eotaxin gene

Joint Linear Filter Design in Multiuser Cooperative Nonregenerative MIMO Relay Systems

This paper addresses the filter design issues for multiuser cooperative nonregenerative MIMO relay systems in both downlink and uplink scenarios. Based on the formulated signal model, the filter matrix optimization is first performed for direct path and relay path respectively, aiming to minimize the mean squared error (MSE). To be more specific, for the relay path, we derive the local optimal filter scheme at the base station and the relay station jointly in the downlink scenario along with a more practical suboptimal scheme, and then a closed-form joint local optimal solution in the uplink scenario is exploited. Furthermore, the optimal filter for the direct path is also presented by using the exiting results of conventional MIMO link. After that, several schemes are proposed for cooperative scenario to combine the signals from both paths. Numerical results show that the proposed schemes can reduce the bit error rate (BER) significantly

Exotic behavior of elastic scattering differential cross-sections of weakly bound nucleus F-17 at small angles

The differential cross-sections for elastic scattering of F-17 and O-17 on Pb-208 have been measured at Radioactive Ion Beam Line at Lanzhou (RIBLL). The variation of the logarithms of differential cross-sections with the square of scattering angles shows clearly that there exists a turning point in the range of small scattering angles (6 degrees-20 degrees) for F-17 having exotic structure, while no turning point was observed in the O-17 elastic scattering. The experimental results have been compared with previous data. Systematical analysis on the available data seems to conclude that there is an exotic behavior of elastic scattering differential cross-sections of weakly bound nuclei with halo or skin structure as compared with that of the ordinary nuclei near stable line. Therefore the fact that the turning point of the logarithms of differential cross-sections appears at small angle for weakly bound nuclei could be used as a new probe to investigate the halo and skin phenomenon