Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha

Accumulation of misfolded protein in the endoplasmic reticulum (ER) triggers an adaptive stress response-termed the unfolded protein response (UPR)-mediated by the ER transmembrane protein kinase and endoribonuclease inositol-requiring enzyme-1alpha (IRE1alpha). We investigated UPR signaling events in mice in the absence of the proapoptotic BCL-2 family members BAX and BAK [double knockout (DKO)]. DKO mice responded abnormally to tunicamycin-induced ER stress in the liver, with extensive tissue damage and decreased expression of the IRE1 substrate X-box-binding protein 1 and its target genes. ER-stressed DKO cells showed deficient IRE1alpha signaling. BAX and BAK formed a protein complex with the cytosolic domain of IRE1alpha that was essential for IRE1alpha activation. Thus, BAX and BAK function at the ER membrane to activate IRE1alpha signaling and to provide a physical link between members of the core apoptotic pathway and the UPR.     

Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR

Human immunodeficiency virus type 1 (HIV-1) gene expression is activated by Tat, a virally encoded protein. Tat trans-activation requires viral (trans-activation--responsive; TAR) RNA sequences located in the R region of the long terminal repeat (LTR). Existing evidence suggests that Tat probably cooperates with cellular factors that bind to TAR RNA in the overall trans-activation process. A HeLa complementary DNA was isolated and characterized that encodes a TAR RNA-binding protein (TRBP). TRBP activated the HIV-1 LTR and was synergistic with Tat function.     

A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response

Intracellular pathogens such as Listeria monocytogenes subvert cellular functions through the interaction of bacterial effectors with host components. Here we found that a secreted listerial virulence factor, LntA, could target the chromatin repressor BAHD1 in the host cell nucleus to activate interferon (IFN)-stimulated genes (ISGs). IFN-λ expression was induced in response to infection of epithelial cells with bacteria lacking LntA; however, the BAHD1-chromatin associated complex repressed downstream ISGs. In contrast, in cells infected with lntA-expressing bacteria, LntA prevented BAHD1 recruitment to ISGs and stimulated their expression. Murine listeriosis decreased in BAHD1(+/-) mice or when lntA was constitutively expressed. Thus, the LntA-BAHD1 interplay may modulate IFN-λ-mediated immune response to control bacterial colonization of the host.     

Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response

The BRCT repeats of the breast and ovarian cancer predisposition protein BRCA1 are essential for tumor suppression. Phosphopeptide affinity proteomic analysis identified a protein, Abraxas, that directly binds the BRCA1 BRCT repeats through a phospho-Ser-X-X-Phe motif. Abraxas binds BRCA1 to the mutual exclusion of BACH1 (BRCA1-associated C-terminal helicase) and CtIP (CtBP-interacting protein), forming a third type of BRCA1 complex. Abraxas recruits the ubiquitin-interacting motif (UIM)-containing protein RAP80 to BRCA1. Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation, and the UIM domains alone were capable of foci formation. The RAP80-Abraxas complex may help recruit BRCA1 to DNA damage sites in part through recognition of ubiquitinated proteins.     

PRRSV体外感染PAMs对IFN-γ mRNA转录水平的影响

\t\t\t\t\t目的\t\t\t\t\t为探讨猪繁殖与呼吸综合征病毒（PRRSV）体外感染猪肺泡巨噬细胞（PAMs）后对IFN-γ及其关键信号分子IRF3和IRF7 mRNA转录的影响。\t\t\t\t\t\t\t\t\t\t\t\t\t方法\t\t\t\t\t从健康仔猪肺脏中无菌分离PAMs,分为对照组和 PRRSV组,于PRRSV感染后的6、12、24、48和60 h收集各组PAMs及其上清液,应用ELISA检测细胞培养上清液中IFN-γ的质量浓度和荧光定量 PCR检测不同组中PRRSV、IFN-γ、IRF3和IRF7的 mRNA转录情况。\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t结果\t\t\t\t\tPRRSV组IFN-γ的质量浓度与正常对照组相比无显著性差异;与对照组相比,PRRSV组IFN-γ mRNA转录量在24 h和48 h显著升高（P<0.01）、48h后降低,IRF3（P<0.05）和IRF7（P<0.01）mRNA转录水平在60 h显著降低。\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t结论\t\t\t\t\tPRRSV感染PAMs过程中对IFN-γ mRNA的转录呈现先抑制再激活后抑制的现象,在一定程度上是通过调控IRF3和IRF7的转录水平来实现的。\t\t\t\t\t\t\t\t\t