Create and preserve: Proteostasis in development and aging is governed by Cdc48/p97/VCP
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- 作者：Andr茅 Franz ; Leena Ackermann ; Thorsten Hoppe
- 关键词：AAA ; ATPase associated with diverse cellular activities ; AD ; Alzheimer's disease ; ALS ; amyotrophic lateral sclerosis ; AMPK ; adenosine monophosphate activated kinase ; Cdc48/CDC-48 ; cell division cycle protein 48 ; DUB ; de-ubiquitylating enzyme ; ERAD ; endoplasmic reticulum-associated degradation ; HD ; Huntington's disease ; IBMPFD ; inclusion body myopathy with Paget's disease of bone and frontotemporal dementia ; MAD ; mitochondria-associated degradation ; MJD ; Machado&ndash ; Joseph disease ; OMM ; outer m
- 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
- 出版年：January, 2014
- 年：2014
- 卷：1843
- 期：1
- 页码：205-215
- 全文大小：650 K
文摘
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.