Fungal pores feel the pull S teinberg et al. report that fungi use motor proteins to distribute their nuclear pores around the nuclear envelope. In animal cells, the nuclear lamina holds the nuclear pores in place, ensuring that they are evenly spaced. The lamina prevents nuclear pores from clustering, promoting import of cargoes through the pores and helping to organize the chromosomes, which ...

There exists a family of currently untreatable, serious human diseases that arise from the inappropriate misfolding and aggregation of extracellular proteins. At present our understanding of mechanisms that operate to maintain proteostasis in extracellular body fluids is limited, but it has significantly advanced with the discovery of a small but growing family of constitutively secreted extrac...

C ells often weigh confl icting signals. They do so in part, say Kevin Janes, Peter Sorger (MIT, Cambridge, MA), and colleagues, by generating extracellular signaling circuits that allow for group consensus. The MIT group measured 19 signaling markers over 13 time points after cells were stimulated with different combinations of proapoptotic TNF and mitogenic insulin and EGF. The data were plot...

Chaperone function plays a key role in repairing proteotoxic damage, in the maintenance of cell architecture, and in cell survival. Here, we summarize our current knowledge about changes in chaperone expression and function in the aging process, as well as their involvement in longevity and cellular senescence.

One of the most successful approaches in the synthesis of inhibitors of t he g lycosidases i s t he s ubstitution of t he e ndocyclic ox ygen i n monosaccharides by a nitrogen atom to get iminosugars. Given that many diseases h ave t heir o rigin i n t he malfunctioning of t hese e nzymes, t his glycomimetics bear s trong p otential a s dr ug c andidates. A t th eir p rotonated state, iminosuga...

Protein homeostasis (proteostasis) requires the timely degradation of misfolded proteins and their aggregates by protein quality control (PQC), of which molecular chaperones are an essential component. Compared with other cell types, PQC in neurons is particularly challenging because they have a unique cellular structure with long extensions. Making it worse, neurons are postmitotic, i.e., cann...

A EuroConference/EMBO workshop on molecular chaperones was held May 26–31, 2001, at Sant Feliu de Guixols, Spain, drenched in the sunshine of the Costa Brava with Salvador Dali’s last home and a museum of his work close at hand. Suitably, the cover of the abstract book displayed a detail from one of Dali’s works, featuring a fried egg hanging by its neck. The meeting covered quite a spectrum of...

Molecular chaperones are essential proteins that participate in the regulation of steroid receptors in eukaryotes. The steroid aporeceptor complex contains the molecular chaperones Hsp90 and Hsp70, p48, the cyclophilin Cyp-40, and the associated proteins p23 and p60. In vitro folding assays showed that Cyp-40 and p23 functioned as molecular chaperones in a manner similar to that of Hsp90 or Hsp...

Molecular chaperones are known to facilitate cellular protein folding. They bind non-native proteins and orchestrate the folding process in conjunction with regulatory cofactors that modulate the affinity of the chaperone for its substrate. However, not every attempt to fold a protein is successful and chaperones can direct misfolded proteins to the cellular degradation machinery for destructio...

Some heat shock proteins HSPs, act as molecular chaperones. These and other molecular chaperones that are not HSPs, function in a variety of protein biosynthetic event and protect proteins from the deleterious effects of stressors by stabilizing, and refolding proteins. They assist protein folding, assembly, transport and degradation. Several human diseases such as neurodegeneration, cancer, ag...