In a recent paper in Traffic, Lene Malerød, a postdoc in Stenmark’s lab, shows that the ESCRT-II complex is required for degradation of ubiquitinated epidermal growth factor receptor and chemokine receptors. This provides new insight into how growth factor and chemokine receptors are transported intracellularly and identifies a novel potential tumour suppressor complex.
Binding of growth factors and cytokines to their cognate receptors on cell membranes triggers their endocytosis and degradation in lysosomes, thus providing a physiologically important negative feedback mechanism for cell signalling.
The ESCRT-II complex recognizes ubiquitinated receptors in the endosomal membrane, thus initiating their sorting to degradative lysosomes. (click to enlarge image)It is not known in detail how endocytosed receptors are trafficked to the degradative lysosomes, but work in Harald StenmarkÂ’s lab has uncovered several factors involved in this process. Among these are the so-called endosomal sorting complexes required for transport (ESCRTs), and Thomas Slagsvold in StenmarkÂ’s group has previously shown that the so-called GLUE domain in the ESCRT-II complex binds ubiquitin .
In a recent paper in Traffic, Lene Malerød, a postdoc in Stenmark’s lab, shows that the ESCRT-II complex is required for degradation of ubiquitinated epidermal growth factor receptor and chemokine receptors. This provides new insight into how growth factor and chemokine receptors are transported intracellularly and identifies a novel potential tumour suppressor complex.
From major journals, first or last author from the Institute for Cancer Research
Lingelem ABD, Kavaliauskiene S, Halsne R, Klokk TI, Surma MA, Klose C, Skotland T, Sandvig K(2020) Diacylglycerol kinase and phospholipase D inhibitors alter the cellular lipidome and endosomal sorting towards the Golgi apparatus Cell Mol Life Sci(in press) DOI 10.1007/s00018-020-03551-6, PubMed 32447426
Skotland T, Kavaliauskiene S, Sandvig K(2020) The role of lipid species in membranes and cancer-related changes Cancer Metastasis Rev DOI 10.1007/s10555-020-09872-z, PubMed 32314087
Lingelem ABD, Kavaliauskiene S, Halsne R, Klokk TI, Surma MA, Klose C, Skotland T, Sandvig K(2020) Diacylglycerol kinase and phospholipase D inhibitors alter the cellular lipidome and endosomal sorting towards the Golgi apparatus Cell Mol Life Sci(in press) DOI 10.1007/s00018-020-03551-6, PubMed 32447426
Fleten KG, Lund-Andersen C, Waagene S, Abrahamsen TW, Mørch Y, Boye K, Torgunrud A, Flatmark K(2020) Experimental Treatment of Mucinous Peritoneal Metastases Using Patient-Derived Xenograft Models Transl Oncol, 13(8), 100793(in press) DOI 10.1016/j.tranon.2020.100793, PubMed 32447231
Hauge A, Rofstad EK(2020) Antifibrotic therapy to normalize the tumor microenvironment J Transl Med, 18(1), 207 DOI 10.1186/s12967-020-02376-y, PubMed 32434573
