https://scholars.lib.ntu.edu.tw/handle/123456789/416524
Title: | Mutant p53 amplifies a dynamin-1/APPL1 endosome feedback loop that regulates recycling and migration | Authors: | Lakoduk, Ashley M Roudot, Philippe Mettlen, Marcel Grossman, Heather M Schmid, Sandra L PING-HUNG CHEN |
Issue Date: | 3-Jun-2019 | Publisher: | ROCKEFELLER UNIV PRESS | Journal Volume: | 218 | Journal Issue: | 6 | Start page/Pages: | 1928 | Source: | The Journal of cell biology | Abstract: | Multiple mechanisms contribute to cancer cell progression and metastatic activity, including changes in endocytic trafficking and signaling of cell surface receptors downstream of gain-of-function (GOF) mutant p53. We report that dynamin-1 (Dyn1) is up-regulated at both the mRNA and protein levels in a manner dependent on expression of GOF mutant p53. Dyn1 is required for the recruitment and accumulation of the signaling scaffold, APPL1, to a spatially localized subpopulation of endosomes at the cell perimeter. We developed new tools to quantify peripherally localized early endosomes and measure the rapid recycling of integrins. We report that these perimeter APPL1 endosomes modulate Akt signaling and activate Dyn1 to create a positive feedback loop required for rapid recycling of EGFR and β1 integrins, increased focal adhesion turnover, and cell migration. Thus, Dyn1- and Akt-dependent perimeter APPL1 endosomes function as a nexus that integrates signaling and receptor trafficking, which can be co-opted and amplified in mutant p53-driven cancer cells to increase migration and invasion. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/416524 | ISSN: | 0021-9525 1540-8140 |
DOI: | https://api.elsevier.com/content/abstract/scopus_id/85067213116 10.1083/jcb.201810183 |
SDG/Keyword: | adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1; beta1 integrin; dynamin I; early endosome antigen 1; epidermal growth factor receptor; messenger RNA; mutant protein; myosin VI; protein kinase B; protein p53; unclassified drug; APPL1 protein, human; beta1 integrin; dynamin I; EGFR protein, human; epidermal growth factor receptor; protein p53; signal transducing adaptor protein; TP53 protein, human; Akt signaling; animal cell; Article; cancer cell; cell invasion; cell migration; controlled study; embryo; endocytosis; endosome; feedback system; focal adhesion; gain of function mutation; human; human cell; mouse; nonhuman; phenotype; priority journal; protein expression; protein function; protein metabolism; quantitative analysis; upregulation; cell adhesion; cell membrane; cell motion; endosome; genetics; lung tumor; metabolism; mutation; non small cell lung cancer; pathology; physiological feedback; protein transport; signal transduction; tumor cell culture; Adaptor Proteins, Signal Transducing; Carcinoma, Non-Small-Cell Lung; Cell Adhesion; Cell Membrane; Cell Movement; Dynamin I; Endocytosis; Endosomes; ErbB Receptors; Feedback, Physiological; Humans; Integrin beta1; Lung Neoplasms; Mutation; Protein Transport; Signal Transduction; Tumor Cells, Cultured; Tumor Suppressor Protein p53 |
Appears in Collections: | 生物化學暨分子生物學科研究所 |
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