Regulation of p53 levels by the E1B 55-kilodalton protein and E4orf6 in adenovirus-infected cells

The adenovirus type 5 243R E1A protein induces p53-dependent apoptosis in the absence of the 19- and 55-kDa E1B polypeptides. This effect appears to result from an accumulation of p53 protein and is unrelated to expression of E1B products. We now report that in the presence of the E1B 55-kDa polypeptide, the 289R E1A protein does not induce such p53 accumulation and, in fact, is able to block that induced by E1A 243R. This inhibition also requires the 289R-dependent transactivation of E4orf6 expression. E4orf6 is known to form complexes with the E1B 55-kDa protein and to function both in the transport and stabilization of viral mRNA and in shutoff of host cell protein synthesis. We demonstrated that the block in p53 accumulation is not due to the generalized shutoff of host cell metabolism. Rather, it appears to result from a mechanism targeted specifically to p53, most likely involving a decrease in the stability of p53 protein. The E1B 55-kDa protein is known to interact with both E4orf6 and p53, and as demonstrated recently by others, we showed that E4orf6 also binds directly to p53. Thus, multiple interactions between all three proteins may regulate p53 stability, resulting in the maintenance of low levels of p53 following virus infection.     

CNP overexpression induces aberrant oligodendrocyte membranes and inhibits MBP accumulation and myelin compaction

2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP) is highly enriched in myelin-forming cells where it is concentrated at the cytoplasmic side of all surface membranes except those of compact myelin. Previous studies have provided evidence that CNP is functionally involved in migration or expansion of membranes during myelination. This hypothesis is supported, in part, by the production of aberrant myelin membranes in transgenic mice that have a 6-fold increase in CNP expression. In addition, many myelin lamellae in these CNP-overexpressing mice lacked major dense lines (MDLs). The purpose of the present study was to determine if CNP overexpression altered: (1) oligodendrocyte and myelin membrane production during early stages of myelination, and (2) the ultrastructural distribution of CNP and myelin basic protein (MBP) in myelin membranes. We identified aberrant membrane expanses that extended from premyelinating oligodendrocyte processes, the periaxonal membrane, and the contact point between oligodendrocyte processes and myelin internodes. Myelin membranes without MDLs were deficient in MBP and enriched in CNP. These data support a functional role for CNP during oligodendrocyte membrane expansion and indicate, for the first time, that CNP may help target MBP to compact myelin.     

Study of susceptibility-induced artefacts in GRASE with different echo train length

The aim of this study was to evaluate the sensitivity of gradient-and-spin-echo (GRASE) sequences to susceptibility effects. GRASE sequences with 21 and 33 echoes per echo train were compared with a T2-weighted FSE sequence with an echo train length of 5 by means of MRI in phantoms, volunteers (n = 10), and patients (n = 19) with old hemorrhagic brain lesions. All experiments were performed on a 1.0-T clinical MR system (Impact Expert, Siemens AG, Erlangen, Germany) with constant imaging parameters. Contrast-to-noise ratios (CNRs) of tubes doped with iron oxides at different concentrations, of brain areas with physiological iron deposition (red nucleus, substantia nigra), and of areas of old brain hemorrhage were calculated for FSE and GRASE pulse sequences. Areas of old brain hemorrhage were also qualitatively analyzed for the degree of visible susceptibility effects by blinded reading. The CNR of iron oxide tubes and iron-containing brain areas decreased with increasing echo trains of GRASE sequences. The CNR of GRASE sequences decreased when compared with CNR of their FSE counterparts (GRASE 21 echo trains 23.8 +/- 0.8, FSE 5 echo trains 26.7 +/- 0.9; p 相似文献   

Insights into T cell development and signal transduction provided by TCR-zeta chain deficient mice

The T cell antigen receptor (TCR) transduces signals that mediate different responses depending on the stage of development of the T cell and the nature of the ligand it engages. The presence of multiple signal transducing subunits (CD3-gamma-delta,-epsilon and zeta chain) suggests the potential to control these responses by altering the subunit composition of the TCR. zeta chain represents an especially important signalling molecule as it contains multiple signalling motifs within its cytoplasmic tail. The generation and analysis of zeta deficient (zeta-/-) and zeta-transgenic mice has provided insight into the role of zeta as well as the CD3 subunits in TCR surface expression, T cell activation and thymocyte development. Herein, we discuss the results from such experiments which suggest distinct roles for zeta chain and the CD3 components at different stages of T cell development.