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

Y1 - 2014

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

VL - 1843

SP - 205

EP - 215

JO - Biochimica et Biophysica Acta - Reviews on Cancer

JF - Biochimica et Biophysica Acta - Reviews on Cancer

SN - 0304-419X

IS - 1

ER -