Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/149077
Title: A novel function of AAA-ATPase p97/VCP in the regulation of cell motility
Authors: Khong, Nicole Zi Jia
Lai, Soak-Kuan
Koh, Cheng-Gee
Geifman-Shochat, Susana
Li, Hoi-Yeung
Keywords: Science::Biological sciences
Issue Date: 2020
Source: Khong, N. Z. J., Lai, S., Koh, C., Geifman-Shochat, S. & Li, H. (2020). A novel function of AAA-ATPase p97/VCP in the regulation of cell motility. Oncotarget, 11(1), 74-85. https://dx.doi.org/10.18632/oncotarget.27419
Project: RG44/13
RG44/16
Journal: Oncotarget
Abstract: High level of the multifunctional AAA-ATPase p97/VCP is often correlated to the development of cancer; however, the underlying mechanism is not understood completely. Here, we report a novel function of p97/VCP in actin regulation and cell motility. We found that loss of p97/VCP promotes stabilization of F-actin, which cannot be reversed by actin-destabilizing agent, Cytochalasin D. Live-cell imaging demonstrated reduced actin dynamics in p97/VCP-knockdown cells, leading to compromised cell motility. We further examined the underlying mechanism and found elevated RhoA protein levels along with increased phosphorylation of its downstream effectors, ROCK, LIMK, and MLC upon the knockdown of p97/VCP. Since p97/VCP is indispensable in the ubiquitination-dependent protein degradation pathway, we investigated if the loss of p97/VCP hinders the protein degradation of RhoA. Knockdown of p97/VCP resulted in a higher amount of ubiquitinated RhoA, suggesting p97/VCP involvement in the proteasome-dependent protein degradation pathway. Finally, we found that p97/VCP interacts with FBXL19, a molecular chaperone known to guide ubiquitinated RhoA for proteasomal degradation. Reduction of p97/VCP may result in the accumulation of RhoA which, in turn, enhances cytoplasmic F-actin formation. In summary, our study uncovered a novel function of p97/VCP in actin regulation and cell motility via the Rho-ROCK dependent pathway which provides fundamental insights into how p97/VCP is involved in cancer development.
URI: https://hdl.handle.net/10356/149077
ISSN: 1949-2553
DOI: 10.18632/oncotarget.27419
Rights: © Khong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

Files in This Item:
File Description SizeFormat 
27419-1047140-1-PB.pdf7.58 MBAdobe PDFView/Open

Page view(s)

118
Updated on Jan 23, 2022

Download(s)

6
Updated on Jan 23, 2022

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.