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The complex of Fas-associated factor 1 with Hsp70 stabilizes the adherens junction integrity by suppressing RhoA activation 被引量:1
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作者 Soonhwa song joon Kyu Park +7 位作者 Sang Chui Shin Jae-Jin Lee Seung Kon Hong In-Kang song Bokyung Kim eun joo song Kong-joo Lee eunice eunKyeong Kim 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2022年第6期14-29,共16页
Fas-associated factor 1 (FAF1) is a scaffolding protein that plays multiple functions, and dysregulation of FAF1 is associated withmany types of diseases such as cancers. FAF1 contains multiple ubiquitin-related domai... Fas-associated factor 1 (FAF1) is a scaffolding protein that plays multiple functions, and dysregulation of FAF1 is associated withmany types of diseases such as cancers. FAF1 contains multiple ubiquitin-related domains (UBA, UBL1, UBL2, UAS, and UBX), eachdomain interacting with a specific partner. In particular, the interaction of UBL1 with heat shock protein 70 (Hsp70) is associatedwith tumor formation, although the molecular understanding remains unknown. In this study, the structural analysis revealed thatHis160 of FAF1 is important for its interaction with Hsp70. The association of Hsp70 with FAF1 is required for the interaction withIQGAP1. FAF1 negatively regulates RhoA activation by FAF1–Hsp70 complex formation, which then interacts with IQGAP1. Thesesteps play a key role in maintaining the stability of cell-to-cell junction. We conclude that FAF1 plays a critical role in the structureand function of adherens junction during tissue homeostasis and morphogenesis by suppressing RhoA activation, which induces theactivation of Rho-associated protein kinase, phosphorylation of myosin light chain, formation of actin stress fiber, and disruptionof adherens junction. In addition, depletion of FAF1 increased collective invasion in a 3D spheroid cell culture. These results provideinsightinto how the FAF1–Hsp70 complex acts as a novelregulator ofthe adherens junction integrity. The complex can be a potentialtherapeutic target to inhibit tumorigenesis and metastasis. 展开更多
关键词 human Fas-associated factor 1(FAF1) heat shock protein 70(Hsp70) adherens junction RhoA activation IQGAP1 X-ray crystallography FAF1–Hsp70 complex
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