CaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation
| Autor: | James F. Burrows, Emma Evergren, Frank Stein, Mandy Rettel, Ian G. Mills, Lorna M. Stewart, Lisa Gerner |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Amino Acid Motifs Immunology Golgi Apparatus Calcium-Calmodulin-Dependent Protein Kinase Kinase Article Coat Protein Complex I Minor Histocompatibility Antigens Cellular and Molecular Neuroscience symbols.namesake Protein Domains SDG 3 - Good Health and Well-being Cell Line Tumor Neoplasms Organelle Golgi Autophagy Homeostasis Humans Endomembrane system Amino Acid Sequence RNA Small Interfering Transport Vesicles Protein kinase A Conserved Sequence Cell Proliferation CAMKK2 Prostate cancer QH573-671 Cell growth Chemistry Cell Biology COPI Golgi apparatus Ribonucleoproteins Small Nuclear Cell biology Unfolded Protein Response Unfolded protein response symbols Lysosomes Peptides Cytology Acids Protein Binding |
| Zdroj: | Stewart, L M, Gerner, L, Rettel, M, Stein, F, Burrows, J F, Mills, I G & Evergren, E 2021, ' CaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation ', Cell, Death & Disease, vol. 12, no. 11, 1040 . https://doi.org/10.1038/s41419-021-04335-x Cell Death and Disease, Vol 12, Iss 11, Pp 1-12 (2021) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) regulates cell and whole-body metabolism and supports tumorigenesis. The cellular impacts of perturbing CAMKK2 expression are, however, not yet fully characterised. By knocking down CAMKK2 levels, we have identified a number of significant subcellular changes indicative of perturbations in vesicle trafficking within the endomembrane compartment. To determine how they might contribute to effects on cell proliferation, we have used proteomics to identify Gemin4 as a direct interactor, capable of binding CAMKK2 and COPI subunits. Prompted by this, we confirmed that CAMKK2 knockdown leads to concomitant and significant reductions in δ-COP protein. Using imaging, we show that CAMKK2 knockdown leads to Golgi expansion, the induction of ER stress, abortive autophagy and impaired lysosomal acidification. All are phenotypes of COPI depletion. Based on our findings, we hypothesise that CAMKK2 sustains cell proliferation in large part through effects on organelle integrity and membrane trafficking. |
| Databáze: | OpenAIRE |
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