[Abstract unavailable

The tetraspanins associate with various surface molecules and with each other to build a network of molecular interactions, the tetraspanin web. The interaction of tetraspanins with each other seems to be central for the assembly of the tetraspanin web. All tetraspanins studied, CD9, CD37, CD53, CD63, CD81, CD82 and CD151, were found to incorporate [ 3 H]palmitate. By site-directed mutagenesis, CD9 was found to be palmitoylated at any of the four internal juxtamembrane regions. The palmitoylation of CD9 did not influence the partition in detergent-resistant membranes but contributed to the interaction with CD81 and CD53. In particular, the resistance of the CD9/CD81 interaction to EDTA, which disrupts other tetraspanin/tetraspanin interactions, was entirely dependent on palmitoylation. ß

No abstract

By interacting with each others, the tetraspanins are thought to assemble a network of molecular interactions, the tetraspanin web. These tetraspanin/tetraspanin interactions involve in part the palmitoylation of the proteins. We show that tetraspanins interact with cholesterol as indicated by the precipitation of tetraspanin/tetraspanin complexes by digitonin, a cholesterol-precipitating reagent, and the labeling of the tetraspanins CD9, CD81 and CD82 with a photoactivatable cholesterol in vivo. Cholesterol may participate to the interaction of tetraspanins with each other since digitonin-precipitation of tetraspanins was correlated with their mutual interaction, and because these interactions were disrupted following cholesterol depletion by methyl-g -cyclodextrin (M g CD) treatment, or cholesterol sequestration by saponin. A mutant CD9 molecule lacking all palmitoylation sites was not precipitated by digitonin under conditions in which wild-type CD9 was precipitated, indicating a role of palmitoylation for the interaction with cholesterol. Finally, upon ligation of tetraspanins on the surface of a lymphoid B cell line, the tyrosine phosphorylation of several proteins, including the vav nucleotide exchange factor, was inhibited when cells were pretreated with M g CD, and increased when they were treated with M g CD/cholesterol complexes. Thus, there is a physical and functional link between tetraspanins and cholesterol.

Tumour cells endure both oncogenic and environmental stresses during cancer progression. Transformed cells must meet increased demands for protein and lipid production needed for rapid proliferation and must adapt to exist in an oxygen‐ and nutrient‐deprived environment. To overcome such challenges, cancer cells exploit intrinsic adaptive mechanisms such as the unfolded protein response (UPR). The UPR is a pro‐survival mechanism triggered by accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER), a condition referred to as ER stress. IRE1, PERK and ATF6 are three ER anchored transmembrane receptors. Upon induction of ER stress, they signal in a coordinated fashion to re‐establish ER homoeostasis, thus aiding cell survival. Over the past decade, evidence has emerged supporting a role for the UPR in the establishment and progression of several cancers, including breast cancer, prostate cancer and glioblastoma multiforme. This review discusses our current knowledge of the UPR during oncogenesis, tumour growth, metastasis and chemoresistance.