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
Lund-Andersen C, Torgunrud A, Kanduri C, Dagenborg VJ, Frøysnes IS, Larsen MM, Davidson B, Larsen SG, Flatmark K(2024) Novel drug resistance mechanisms and drug targets in BRAF-mutated peritoneal metastasis from colorectal cancer J Transl Med, 22(1), 646 DOI 10.1186/s12967-024-05467-2, PubMed 38982444
Hammer Q, Perica K, Mbofung RM, van Ooijen H, Martin KE, Momayyezi P, Varady E, Pan Y, Jelcic M, Groff B, Abujarour R, Krokeide SZ, Lee T, Williams A, Goodridge JP, Valamehr B, Önfelt B, Sadelain M, Malmberg KJ(2024) Genetic ablation of adhesion ligands mitigates rejection of allogeneic cellular immunotherapies Cell Stem Cell(in press) DOI 10.1016/j.stem.2024.06.011, PubMed 38981470
Andresen NK, Røssevold AH, Borgen E, Schirmer CB, Gilje B, Garred Ø, Lømo J, Stensland M, Nordgård O, Falk RS, Mathiesen RR, Russnes HG, Kyte JA, Naume B(2024) Circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors - a biomarker analysis of the ALICE and ICON trials Mol Oncol(in press) DOI 10.1002/1878-0261.13675, PubMed 38978352
Lê Quý K, Chernigovskaya M, Stensland M, Singh S, Leem J, Revale S, Yadin DA, Nice FL, Povall C, Minns DH, Galson JD, Nyman TA, Snapkow I, Greiff V(2024) Benchmarking and integrating human B-cell receptor genomic and antibody proteomic profiling NPJ Syst Biol Appl, 10(1), 73 DOI 10.1038/s41540-024-00402-z, PubMed 38997321
Lund-Andersen C, Torgunrud A, Kanduri C, Dagenborg VJ, Frøysnes IS, Larsen MM, Davidson B, Larsen SG, Flatmark K(2024) Novel drug resistance mechanisms and drug targets in BRAF-mutated peritoneal metastasis from colorectal cancer J Transl Med, 22(1), 646 DOI 10.1186/s12967-024-05467-2, PubMed 38982444
Andresen NK, Røssevold AH, Borgen E, Schirmer CB, Gilje B, Garred Ø, Lømo J, Stensland M, Nordgård O, Falk RS, Mathiesen RR, Russnes HG, Kyte JA, Naume B(2024) Circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors - a biomarker analysis of the ALICE and ICON trials Mol Oncol(in press) DOI 10.1002/1878-0261.13675, PubMed 38978352