Metal-organic framework bearing new viologen ligand for ammonia and Cr2O7 2- sensing.

Three anionic metal-organic frameworks (MOFs) {[Zn3(BTEC)2(H2O)(4-BCBPY)]·(H2O)} n (1-3) (BTEC4- = 1,2,4,5-benzenetetracarboxylic acid anion, 4-BCBPY2+ = 1,1'-bis(4-cyanobenzyl)-4,4'-bipyridinium dication) were synthesized in the reaction of 1,2,4,5-benzenetetracarboxylic acid with different metal salts such as ZnNO3, ZnCl2, and ZnSO4, under solvothermal conditions in the presence of 1,1'-bis(4-cyanobenzyl)-4,4'-bipyridinium chloride. Single crystal X-ray diffraction analysis shows that compounds 1, 2 and 3 have MOF structures based on binuclear metal building units, which are connected by two protonated BTEC4- ligands and three zinc ions, and the viologen cation 4-BCBPY2+ is located in the channel to achieve charge balance. Compounds 1, 2 and 3 have good photosensitivity, respond to sunlight, UV light and blue ray, and turn blue. The D-A distance and π-π stacking distance of the discolored samples (1P, 2P and 3P) changed. In addition, the three compounds showed visible color changes to ammonia vapor, rapidly changing from white to blue. At the same time, the three compounds exhibited fluorescence quenching to ammonia vapor and Cr2O7 2-. It is further proved that compounds 1, 2 and 3 are fluorescent sensors with a low detection limit (for Cr2O7 2-: 10-5 M) and high sensitivity for ammonia vapor and Cr2O7 2-. It was found that photochromic behavior, ammonia sensing properties can be tuned by the nature of metal salts.

HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin-proteasome pathway.

The cellular BRCA1 protein level is essential for its tumor suppression activity and is tightly regulated through multiple mechanisms including ubiquitn-proteasome system. E3 ligases are involved to promote BRCA1 for ubiquitination and degradation. Here, we identified HUWE1/Mule/ARF-BP1 as a novel BRCA1-interacting protein involved in the control of BRCA1 protein level. HUWE1 binds BRCA1 through its N-terminus degron domain. Depletion of HUWE1 by siRNA-mediated interference significantly increases BRCA1 protein levels and prolongs the half-life of BRCA1. Moreover, exogenous expression of HUWE1 promotes BRCA1 degradation through the ubiquitin-proteasome pathway, which could explain an inverse correlation between HUWE1 and BRCA1 levels in MCF10F, MCF7 and MDA-MB-231 breast cancer cells. Consistent with a functional role for HUWE1 in regulating BRCA1-mediated cellular response to DNA damage, depletion of HUWE1 by siRNA confers increased resistance to ionizing radiation and mitomycin. These data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis.

HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin-proteasome pathway.

The cellular BRCA1 protein level is essential for its tumor suppression activity and is tightly regulated through multiple mechanisms including ubiquitn-proteasome system. E3 ligases are involved to promote BRCA1 for ubiquitination and degradation. Here, we identified HUWE1/Mule/ARF-BP1 as a novel BRCA1-interacting protein involved in the control of BRCA1 protein level. HUWE1binds BRCA1 through its N-terminus degron domain. Depletion of HUWE1 by siRNA-mediated interference significantly increases BRCA1 protein levels and prolongs the half-life of BRCA1. Moreover, exogenous expression of HUWE1 promotes BRCA1 degradation through the ubiquitin-proteasome pathway, which could explain an inverse correlation between HUWE1 and BRCA1 levels in MCF10F, MCF7 and MDA-MB-231 breast cancer cells. Consistent with a functional role for HUWE1 in regulating BRCA1-mediated cellular response to DNA damage, depletion of HUWE1 by siRNA confers increased resistance to ionizing radiation and mitomycin. These data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis.