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
Bergholtz H, Carter JM, Cesano A, Cheang MCU, Church SE, Divakar P, Fuhrman CA, Goel S, Gong J, Guerriero JL, Hoang ML, Hwang ES, Kuasne H, Lee J, Liang Y, Mittendorf EA, Perez J, Prat A, Pusztai L, Reeves JW, Riazalhosseini Y, Richer JK, Sahin Ö, Sato H, Schlam Iet al.(2021) Best Practices for Spatial Profiling for Breast Cancer Research with the GeoMx® Digital Spatial Profiler Cancers (Basel), 13(17) DOI 10.3390/cancers13174456, PubMed 34503266
Taavitsainen S, Engedal N, Cao S, Handle F, Erickson A, Prekovic S, Wetterskog D, Tolonen T, Vuorinen EM, Kiviaho A, Nätkin R, Häkkinen T, Devlies W, Henttinen S, Kaarijärvi R, Lahnalampi M, Kaljunen H, Nowakowska K, Syvälä H, Bläuer M, Cremaschi P, Claessens F, Visakorpi T, Tammela TLJ, Murtola Tet al.(2021) Single-cell ATAC and RNA sequencing reveal pre-existing and persistent cells associated with prostate cancer relapse Nat Commun, 12(1), 5307 DOI 10.1038/s41467-021-25624-1, PubMed 34489465
Møller P, Sampson JR, Dominguez-Valentin M, Seppälä TT(2021) Towards evidence-based personalised precision medicine for Lynch syndrome Lancet Oncol, 22(9), e383 DOI 10.1016/S1470-2045(21)00400-9, PubMed 34478667
Krzyscik MA, Zakrzewska M, Sørensen V, Øy GF, Brunheim S, Haugsten EM, Mælandsmo GM, Wiedlocha A, Otlewski J(2021) Fibroblast Growth Factor 2 Conjugated with Monomethyl Auristatin E Inhibits Tumor Growth in a Mouse Model Biomacromolecules(in press) DOI 10.1021/acs.biomac.1c00662, PubMed 34542998
