Auswahl der wissenschaftlichen Literatur zum Thema „Sem1/DSS1“

The evolutionarily conserved protein Sem1/Dss1 is a subunit of the regulatory particle (RP) of the proteasome, and, in mammalian cells, binds the tumor suppressor protein BRCA2. Here, we describe a new function for yeast Sem1. We show that sem1 mutants are impaired in messenger RNA (mRNA) export and transcription elongation, and induce strong transcription-associated hyper-recombination phenotypes. Importantly, Sem1, independent of the RP, is functionally linked to the mRNA export pathway. Biochemical analyses revealed that, in addition to the RP, Sem1 coenriches with components of two other multisubunit complexes: the nuclear pore complex (NPC)-associated TREX-2 complex that is required for transcription-coupled mRNA export, and the COP9 signalosome, which is involved in deneddylation. Notably, targeting of Thp1, a TREX-2 component, to the NPC is perturbed in a sem1 mutant. These findings reveal an unexpected nonproteasomal function of Sem1 in mRNA export and in prevention of transcription-associated genome instability. Thus, Sem1 is a versatile protein that might stabilize multiple protein complexes involved in diverse pathways.

Skeletal shape and mechanical properties define, to a large extent, vertebrate morphology and physical capacities. During development, skeletal morphogenesis results from dynamic communications between chondrocytes, osteoblasts, osteoclasts, and other cellular components of the skeleton. Later in life, skeletal integrity depends on the regulatory cascades that assure the equilibrium between bone formation and resorption. Finally, during aging, skeletal catabolism prevails over anabolism resulting in progressive skeletal degradation. These cellular processes depend on the transcriptional cascades that control cell division and differentiation in each cell type. Most Distal-less (Dlx) homeobox transcription factors are directly involved in determining the proliferation and differentiation of chondrocytes and osteoblasts and, indirectly, of osteoclasts. While the involvement of Dlx genes in the regulation of skeletal formation has been well-analyzed thanks to several mutant mouse models, the role of these genes in the maintenance of bone integrity has been only partially studied. The importance of Dlx genes for adult bone tissues is evidenced by their central role in the regulatory pathways involving Osx/Sp7 and Runx2, the two major master genes of osteogenesis. Dlx genes appear to be involved in several bone pathologies including, for example, osteoporosis. Indeed, at least five large-scale GWAS studies which aimed to detect loci associated with human bone mineral density (BMD) have identified a known DLX5/6 regulatory region within chromosome 7q21.3 in proximity of SEM1/FLJ42280/DSS1 coding sequences, suggesting that DLX5/6 expression is critical in determining healthy BMD. This review aims to summarize the major findings concerning the involvement of Dlx genes in skeletal development and homeostasis and their involvement in skeletal aging and pathology.