TY - JOUR
T1 - Create and preserve
T2 - proteostasis in development and aging is governed by Cdc48/p97/VCP
AU - Franz, André
AU - Ackermann, Leena
AU - Hoppe, Thorsten
N1 - Copyright © 2013 Elsevier B.V. All rights reserved.
PY - 2014/1
Y1 - 2014/1
N2 - The AAA-ATPase Cdc48 (also called p97 or VCP) acts as a key regulator in proteolytic pathways, coordinating recruitment and targeting of substrate proteins to the 26S proteasome or lysosomal degradation. However, in contrast to the well-known function in ubiquitin-dependent cellular processes, the physiological relevance of Cdc48 in organismic development and maintenance of protein homeostasis is less understood. Therefore, studies on multicellular model organisms help to decipher how Cdc48-dependent proteolysis is regulated in time and space to meet developmental requirements. Given the importance of developmental regulation and tissue maintenance, defects in Cdc48 activity have been linked to several human pathologies including protein aggregation diseases. Thus, addressing the underlying disease mechanisms not only contributes to our understanding on the organism-wide function of Cdc48 but also facilitates the design of specific medical therapies. In this review, we will portray the role of Cdc48 in the context of multicellular organisms, pointing out its importance for developmental processes, tissue surveillance, and disease prevention. This article is part of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf.
AB - The AAA-ATPase Cdc48 (also called p97 or VCP) acts as a key regulator in proteolytic pathways, coordinating recruitment and targeting of substrate proteins to the 26S proteasome or lysosomal degradation. However, in contrast to the well-known function in ubiquitin-dependent cellular processes, the physiological relevance of Cdc48 in organismic development and maintenance of protein homeostasis is less understood. Therefore, studies on multicellular model organisms help to decipher how Cdc48-dependent proteolysis is regulated in time and space to meet developmental requirements. Given the importance of developmental regulation and tissue maintenance, defects in Cdc48 activity have been linked to several human pathologies including protein aggregation diseases. Thus, addressing the underlying disease mechanisms not only contributes to our understanding on the organism-wide function of Cdc48 but also facilitates the design of specific medical therapies. In this review, we will portray the role of Cdc48 in the context of multicellular organisms, pointing out its importance for developmental processes, tissue surveillance, and disease prevention. This article is part of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf.
KW - Adenosine Triphosphatases/physiology
KW - Aging/genetics
KW - Animals
KW - Cell Cycle Proteins/physiology
KW - Cell Proliferation
KW - Growth and Development/genetics
KW - Humans
KW - Protein Stability
KW - Proteostasis Deficiencies/genetics
KW - Reproduction/physiology
KW - Valosin Containing Protein
U2 - 10.1016/j.bbamcr.2013.03.031
DO - 10.1016/j.bbamcr.2013.03.031
M3 - Review
C2 - 23583830
SN - 0006-3002
VL - 1843
SP - 205
EP - 215
JO - B B A - Reviews on Cancer
JF - B B A - Reviews on Cancer
IS - 1
ER -
