The most important group of genes perhaps is the GANSI genes, most of which show down-regulation in the aged or aged-impaired rats and by themselves usually are not associated with any syndromes. These genes affect various signal transduction pathways and functions in the brain contributing to the disruption of proper learning and memory formation. These GASI and GANSI genes form a set of interesting candidates for future investigations as to how they interact with each other, how they are regulated, and what target genes they may affect in order to elucidate the mechanisms behind aging and age-associated spatial learning impairment. BRE shares no homology with other known gene products. The protein contains two putative ubiquitin E2 variant domains but lacks critical cysteine which is required for ubiquitination. BRE protein is present in both the cytosol and nucleus. In the cytoplasm, BRE binds to the cytoplasmic region of p55 TNF receptors to suppress TNF-a induced activation of NF-kB. 
The protein can also bind to Fas to inhibit the mitochondrial apoptotic pathway. BRE is also found to be a component in BRISC complex that specifically cleaves lysine63-linked ubiquitin. BRE may Butenafine hydrochloride function as a key adaptor protein which assembles the different components of the BRISC complex. In the nucleus, BRE is a component of the DNA damage responsive BRCA1-RAP80 complex. BRE protein acts as an adapter that links the interaction between NBA1 and the rest of the complex. This adapter modulates the ubiquitin E3 ligase activity of the BRCA1/BARD1 complex by interacting with MERIT 40 which enhances cellular survival following DNA damage. BRE has been extensively studied in lung tumour, hepatocellular carcinoma and oesophageal carcinoma showing that it promoted cell survival. Nevertheless, the function of BRE in stem cells has never been investigated. BRE is expressed very early on in embryonic development; at the 2-cell stage, in the inner cell mass cells of blastocysts and even in embryonic stem cells. In this context, we want to establish why BRE was expressed so early in development and whether it was involved in maintaining stemness and cell differentiation. It is generally accepted that stress-responsive genes, like BRE, play a crucial role in biological processes such as cell survival, differentiation, apoptosis and regeneration. To address our questions, we employed HUCPV progenitor cells as our experimental cell model. These cells are normally found in the perivascular regions of human umbilical arteries and vein and contain a rich source of commercially valuable mesenchymal stem cells. The HUCPV cells were found to have a colony forming unitfibroblast frequency of about 1:300, which is far higher than that of bone marrow or umbilical cord blood. Actins, together with intermediate filaments and microtubules, play an important role in cytoskeletal organization and response to external Yunaconitine mechanical stimuli that affect cell differentiation. During differentiation, the cell morphology is almost always altered in respond to integrins, cadherins and cytoskeletal proteins being differentially expressed. When MSCs undergo osteogenesis, the cells become flatten and spread out; while the cells acquire a spherical shape when they undergo chondrogenesis. It has been demonstrated when actin is disrupted by cytochalasin B, chondrogenesis is greatly enhanced in ESCs and MSCs. In contrast, chondrogenesis is hindered under conditions that favour actin assembly. In our study, we demonstrated that the structural integrity of F-actin became dissembled in BRE-silenced HUCPV cells while F-actin structures were very distinctive in cells transfected with Ctl-siRNAs.