View : 250 Download: 72

The complex of Fas-associated factor 1 with Hsp70 stabilizes the adherens junction integrity by suppressing RhoA activation

Title
The complex of Fas-associated factor 1 with Hsp70 stabilizes the adherens junction integrity by suppressing RhoA activation
Authors
Song, SoonhwaPark, Joon KyuShin, Sang ChulLee, Jae-JinHong, Seung KonSong, In-KangKim, BokyungSong, Eun JooLee, Kong-JooKim, Eunice EunKyeong
Ewha Authors
이공주송은주
SCOPUS Author ID
이공주scopusscopus; 송은주scopus
Issue Date
2022
Journal Title
JOURNAL OF MOLECULAR CELL BIOLOGY
ISSN
1674-2788JCR Link

1759-4685JCR Link
Citation
JOURNAL OF MOLECULAR CELL BIOLOGY vol. 14, no. 6
Keywords
human Fas-associated factor 1 (FAF1)heat shock protein 70 (Hsp70)adherens junctionRhoA activationIQGAP1X-ray crystallographyFAF1-Hsp70 complex
Publisher
OXFORD UNIV PRESS
Indexed
SCIE; SCOPUS WOS
Document Type
Article
Abstract
Fas-associated factor 1 (FAF1) is a scaffolding protein that plays multiple functions, and dysregulation of FAF1 is associated with many types of diseases such as cancers. FAF1 contains multiple ubiquitin-related domains (UBA, UBL1, UBL2, UAS, and UBX), each domain interacting with a specific partner. In particular, the interaction of UBL1 with heat shock protein 70 (Hsp70) is associated with tumor formation, although the molecular understanding remains unknown. In this study, the structural analysis revealed that His160 of FAF1 is important for its interaction with Hsp70. The association of Hsp70 with FAF1 is required for the interaction with IQGAP1. FAF1 negatively regulates RhoA activation by FAF1-Hsp70 complex formation, which then interacts with IQGAP1. These steps play a key role in maintaining the stability of cell-to-cell junction. We conclude that FAF1 plays a critical role in the structure and function of adherens junction during tissue homeostasis and morphogenesis by suppressing RhoA activation, which induces the activation of Rho-associated protein kinase, phosphorylation of myosin light chain, formation of actin stress fiber, and disruption of adherens junction. In addition, depletion of FAF1 increased collective invasion in a 3D spheroid cell culture. These results provide insight into how the FAF1-Hsp70 complex acts as a novel regulator of the adherens junction integrity. The complex can be a potential therapeutic target to inhibit tumorigenesis and metastasis.
DOI
10.1093/jmcb/mjac037
Appears in Collections:
약학대학 > 약학과 > Journal papers
Files in This Item:
mjac037.pdf(3.23 MB) Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

BROWSE