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Article Addendum
Tipping the Delicate Balance: Defining How Proteasome Maturation Affects the Degradation of a Substrate for Autophagy and Endoplasmic Reticulum Associated Degradation (ERAD)
Jeffrey L. Brodsky and Craig M. Scott
volume 3 | issue 6
November/December 2007Pages: 623 - 625
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An increasing body of data links endoplasmic reticulum (ER) function to autophagy. Not surprisingly, then, some aberrant proteins in the ER can be destroyed either via ER associated degradation (ERAD), which is proteasome-mediated, or via autophagy. One such substrate is the “Z” variant of the alpha-1 protease inhibitor (A1Pi), variably known as A1Pi-Z or AT-Z (“anti-trypsin, Z variant”). The wild type protein is primarily synthesized in the liver and is secreted. In contrast, AT-Z—like other ERAD substrates—is retro-translocated from the ER and delivered to the proteasome. However, AT-Z can form high molecular weight polymers that are degraded via autophagy, and cells that accumulate AT-Z polymers ultimately succumb, which leads to liver disease. Therefore, identifying genes that have an impact AT-Z turnover represents an active area of research. To this end, a yeast expression system for AT-Z has proven valuable. For example, a recent study using this system indicates that the activity of a proteasome assembly chaperone (PAC) is critical for maximal AT-Z turnover, which suggests a new role for PACs. Because PACs are conserved, it will be critical to analyze whether these dedicated chaperones are implicated in other diseases associated with ERAD and autophagy.
Addendum to:
ADD66, a Gene Involved in the Endoplasmic Reticulum Associated Degradation of a1-Antitrypsin-Z in Yeast, Facilitates Proteasome Activity and Assembly
C.M. Scott, K.B. Kruse, B.Z. Schmidt, D.H. Perlmutter, A.A. McCracken and J.L. Brodsky
Mol Biol Cell 2007; In press
Authors
Jeffrey L. Brodsky
University of Pittsburgh
Craig M. Scott
University of Pittsburgh
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.