Febs Letters

doi: 10.1016/S0014-5793(04)00266-2pmid: N/A

doi: 10.1016/S0014-5793(04)00261-3pmid: N/A

Parisi, Gustavo; Fornasari, Marı́a Silvina; Echave, Julián

doi: 10.1016/S0014-5793(04)00165-6pmid: 15043994

Dynactin is a multimeric protein essential for the minus‐end‐directed transport driven by microtubule‐based motor dynein. The pointed‐end subcomplex in dynactin contains p62, p27, p25, and Arp11 subunits, and is thought to participate in interactions with membranous cargoes. We used sequence and structure prediction analysis to study dynactins p25 and p27. Here we present evidence that strongly supports that dynactins p27 and p25 contain the isoleucine‐patch motif and adopt the left‐handed parallel β‐helix fold. The structural models we obtained could contribute to the understanding of the complex interactions that dynactins are able to establish with cargo particles, microtubules or other dynactin subunits.

Gómez-Muñoz, Antonio

doi: 10.1016/S0014-5793(04)00211-Xpmid: 15069950

Ceramide‐1‐phosphate (Cer‐1‐P) is emerging as a novel bioactive sphingolipid. It is formed by phosphorylation of ceramide catalyzed by ceramide kinase, and has been implicated in different cellular processes. Cer‐1‐P is mitogenic for fibroblasts, blocks apoptosis in macrophages, controls phagocytosis in neutrophils, and mediates inflammatory responses. Only recently have we started to uncover the signaling pathways that are affected by Cer‐1‐P. Recent work has demonstrated that cytosolic phospholipase A2 and acid sphingomyelinase are direct intracellular targets of Cer‐1‐P, and that it may also induce phosphorylation of extracellular signal‐regulated kinase‐2 and calcium mobilization. These actions of Cer‐1‐P seem to be cell type‐specific.

Subbarao Sreedhar, Amere; Kalmár, Éva; Csermely, Péter; Shen, Yu-Fei

doi: 10.1016/S0014-5793(04)00229-7pmid: 15069952

The 90 kDa heat shock protein, Hsp90, is a main functional component of an important cytoplasmic chaperone complex, and it is involved in various cellular processes, such as cell proliferation, differentiation and apoptosis. Identification of Hsp90 as a molecular target of various anticancer drugs highlighted its importance from the clinical point of view. Here we summarize the current knowledge on various Hsp90 isoforms regarding their genomic location, molecular evolution, functional differences, differential induction after various environmental stresses and in pathological conditions as well as the growing importance of discriminating between Hsp90 isoforms in clinical practice.

Mohajeri, M.Hasan; Kuehnle, Katrin; Li, Hong; Poirier, Raphael; Tracy, Jay; Nitsch, Roger M.

doi: 10.1016/S0014-5793(04)00169-3pmid: 15043995

Abnormally high concentrations of β‐amyloid peptide (Aβ) and amyloid plaque formation in Alzheimer's disease (AD) may be caused either by increased generation or by decreased degradation of Aβ. Therefore, activation of mechanisms that lower brain Aβ levels is considered valuable for AD therapy. Neuronal upregulation of neprilysin (NEP) in young transgenic mice expressing the AD‐causing amyloid precursor protein mutations (SwAPP) led to reduction of brain Aβ levels and delayed Aβ plaque deposition. In contrast, a comparable increase of brain NEP levels in aged SwAPP mice with pre‐existing plaque pathology did not result in a significant reduction of plaque pathology. Therefore, we suggest that the potential of NEP for AD therapy is age‐dependent and most effective early in the course of AD pathophysiology.

Yu, Jing; Yu, Xiaomin; Liu, Jianhua

doi: 10.1016/S0014-5793(04)00170-Xpmid: 15043996

The gene CP0718 encoding a putative manganese‐containing superoxide dismutase of Chlamydia pneumoniae AR39 was cloned and expressed in Escherichia coli. Characterization showed that the expressed protein with a monomeric molecular mass of 23.1 kDa had superoxide dismutase (SOD) activity and the cofactor of CpSOD was a bivalent manganese cation. It is unexpected that this enzyme was hyperthermostable, and maintained about 90% activity after incubation at 70°C for 60 min. Manganese binding residues found in the SOD sequences from different species are conserved in CpSOD. Bioinformatics analysis compared with Propionibacterium shermanii MnSOD was performed to elucidate the CpSOD hyperthermostability based on amino acid sequences.

Crispi, Stefania; Sanzari, Emma; Monfregola, Jlenia; De Felice, Nicola; Fimiani, Giorgia; Ambrosio, Raffaele; D'Urso, Michele; Ursini, Matilde Valeria

doi: 10.1016/S0014-5793(04)00166-8pmid: 15043997

We recently published the genomic characterization of the STAT5A and STAT5B paralogous genes that are located head to head in the 17q21 chromosome and share large regions of sequence identity. We here demonstrate by transient in vitro transfection that STAT5A and STAT5B promoters are able to direct comparable levels of transcription. The expression of basal promoters is enhanced after Sp1 up‐regulation in HeLa and SL2 cells while DNA methylation associated to the recruitment of MeCP2 methyl CpG binding protein down‐regulates STAT5A and B promoters by interfering with Sp1‐induced transcription. In addition, cross‐species sequence comparison identified a bi‐directional negative cis‐acting regulatory element located in the STAT5 intergenic region.

Cappelletti, Graziella; Tedeschi, Gabriella; Maggioni, Maria G.; Negri, Armando; Nonnis, Simona; Maci, Rosalba

doi: 10.1016/S0014-5793(04)00173-5pmid: 15043998

Tyrosine nitration of proteins is emerging as a post‐translational modification playing a role in physiological conditions. Looking for the molecular events triggered by nitric oxide in nerve growth factor‐induced neuronal differentiation, we now find that nitration occurs on the microtubule‐associated protein τ. In differentiated PC12 cells, we have identified as τ a nitrated protein that co‐immunoprecipitates with α‐tubulin and indicated that the modified protein is associated with the cytoskeleton but it is confined to a restricted cell region. This paper supplies the first evidence that nitration of τ occurs in a physiological process and suggests that it could play a role in neuronal differentiation.

Hernandez-Pigeon, Hélène; Laurent, Guy; Humbert, Odile; Salles, Bernard; Lautier, Dominique

doi: 10.1016/S0014-5793(04)00181-4pmid: 15043999

Mismatch repair plays a critical role in genome stability. This process requires several proteins including hMSH2/hMSH6 (hMutSα) heterodimer involved in the first stage of the process, the mispair recognition. We previously reported that in U937 and HL‐60 cell lines, hMSH2 and hMSH6 protein expression was much lower than that in HeLa and KG1a cells. Here, we showed that the decreased expression of hMutSα results from differences in the degradation rate of both proteins by the ubiquitin‐proteasome pathway. Our data suggest that in human cell lines, ubiquitin‐proteasome could play an important role in the regulation of hMutSα protein expression, thereby regulating mismatch repair activity.