Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/72339
Title: Investigation of the function and behavior of p97/VCP
Authors: Khong, Zi Jia
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2017
Source: Khong, Z. J. (2017). Investigation of the function and behavior of p97/VCP. Doctoral thesis, Nanyang Technological University, Singapore.
Abstract: p97/VCP is a multifunctional ATP-fueled ATPase quintessential for cell survival. As one of the most abundant cytosolic proteins, it is not surprising that p97/VCP regulates numerous pathways to ensure proper cell homeostasis. Here I show that p97/VCP regulates actin dynamics and cell migration via the ROCK pathway. The loss of p97/VCP triggers hyperphosphorylation of ROCK, resulting in extensive polymerization of actin. Persistent F-actin filaments and the absence of essential cell motility-related actin structures in p97/VCP knockdown cells led to compromised cell migration. I found that the loss of p97/VCP increases the level of ROCK-activating kinase, Plk1, through the ubiquitin-proteasome pathway. The increase in Plk1 thereafter affects the phosphorylation status of ROCK. Taken together, my study defines a hitherto unknown role of p97/VCP in actin regulation and describes a mechanism for the phosphorylation-dependent regulation of ROCK activity that implicates cancer metastasis and wound healing.
URI: http://hdl.handle.net/10356/72339
Fulltext Permission: restricted
Fulltext Availability: With Fulltext
Appears in Collections:SBS Theses

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