Nature Cell Biology

doi: 10.1038/ncb0407-355bpmid: N/A

Our competing financial interests policy expands across the journal

doi: 10.1038/ncb0407-355apmid: N/A

Spot-checking figures for manipulation.

Newlon, Carol S.

doi: 10.1038/ncb0407-356pmid: N/A

Russell, David G.

doi: 10.1038/ncb0407-357pmid: 17401383

Dendritic cells are specialized antigen-presenting cells. As such, they exhibit limited degradation of phagocytosed antigens, which favours efficient antigen presentation to T lymphocytes. Work now shows that the restricted proteolysis is due to alkalinization of the phagosome through Rab27a-dependent fusion with a subset of lysosomal vesicles bearing NADPH–oxidase complexes.

Todi, Sokol V.; Paulson, Henry L.

doi: 10.1038/ncb0407-359pmid: 17401384

Nine inherited neurodegenerative disorders are caused by polyglutamine (polyQ) expansions in diverse proteins. A study now suggests that polyQ-mediated depletion of nonhistone chromatin proteins enhances genotoxic stress induced by the disease protein.

Radisky, Derek C.; Bissell, Mina J.

doi: 10.1038/ncb0407-361pmid: 17401385

The detrimental effects of nuclear factor-kappa B (NF-κB) signalling in cancer cells lacking the oestrogen receptor have now become clear, with the demonstration that increased NF-κB levels induce expression of Bcl-2 to both suppress apoptosis and induce epithelial–mesenchymal transitions (EMTs).

Lees-Miller, Susan P.

doi: 10.1038/ncb0407-363pmid: 17401386

In mammalian cells, DNA double-strand breaks (DSBs) are repaired by the non-homologous end-joining (NHEJ) pathway. A key component of this repair mechanism is the DNA binding protein, Ku. A recent study shows that Par-3, a protein involved in cell polarity and the assembly of tight junctions, interacts with Ku and is involved in NHEJ, suggesting an intriguing new role for Par-3 and links between cell morphology and DNA damage response pathways.

Rosenthal, Christina Karlsson

doi: 10.1038/ncb0407-366pmid: 17401387

Jancic, Carolina; Savina, Ariel; Wasmeier, Christina; Tolmachova, Tanya; El-Benna, Jamel; Dang, Pham My-Chan; Pascolo, Steve; Gougerot-Pocidalo, Maire-Anne; Raposo, Graça; Seabra, Miguel C.; Amigorena, Sebastian

doi: 10.1038/ncb1552

Janiesch, Philipp Christoph; Kim, Johnny; Mouysset, Julien; Barikbin, Roja; Lochmüller, Hanns; Cassata, Giuseppe; Krause, Sabine; Hoppe, Thorsten

doi: 10.1038/ncb1554pmid: 17369820

Protein degradation in eukaryotes often requires the ubiquitin-selective chaperone p97 for substrate recruitment and ubiquitin-chain assembly. However, the physiological relevance of p97, and its role in developmental processes, remain unclear. Here, we discover an unanticipated function for CDC-48/p97 in myosin assembly and myofibril organization, both in Caenorhabditis elegans and humans. The developmentally regulated assembly of a CDC-48–UFD-2–CHN-1 complex links turnover of the myosin-directed chaperone UNC-45 to functional muscle formation. Our data suggest a similarly conserved pathway regulating myosin assembly in humans. Remarkably, mutations in human p97, known to cause hereditary inclusion-body myopathy, abrogate UNC-45 degradation and result in severely disorganized myofibrils, detrimental towards sarcomeric function. These results identify a key role for CDC-48/p97 in the process of myofibre differentiation and maintenance, which is abolished during pathological conditions leading to protein aggregation and inclusion-body formation in human skeletal muscle.