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  3. Biochemistry and Molecular Biology / 生物化學暨分子生物學研究所
  4. Mutant p53 amplifies a dynamin-1/APPL1 endosome feedback loop that regulates recycling and migration
 
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Mutant p53 amplifies a dynamin-1/APPL1 endosome feedback loop that regulates recycling and migration

Journal
The Journal of cell biology
Journal Volume
218
Journal Issue
6
Pages
1928
Date Issued
2019-06-03
Author(s)
Lakoduk, Ashley M
Roudot, Philippe
Mettlen, Marcel
Grossman, Heather M
Schmid, Sandra L
PING-HUNG CHEN  
DOI
https://api.elsevier.com/content/abstract/scopus_id/85067213116
10.1083/jcb.201810183
URI
https://scholars.lib.ntu.edu.tw/handle/123456789/416524
URL
https://api.elsevier.com/content/abstract/scopus_id/85067213116
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.
SDGs

[SDGs]SDG3

Other Subjects
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
Publisher
ROCKEFELLER UNIV PRESS
Type
journal article

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