Regulation of the Copper Chaperone CCS by XIAP-Mediated Ubiquitination

Brady, Graham F.; Galbán, Stefanie; Liu, Xuwen; Basrur, Venkatesha; Gitlin, Jonathan D.; Elenitoba-Johnson, Kojo S.J.; Wilson, Thomas E.; Duckett, Colin S.

doi:10.1128/mcb.00900-09

Cited by 66 publications

(58 citation statements)

References 70 publications

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“…Brady et al (36) showed that, depending on the intracellular copper status, CCS delivers copper either to SOD1 or to XIAP. Under basal conditions, XIAP enhances copper acquisition and delivery to SOD1 by promoting the nondegradative ubiquitination of CCS.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in pEBB-CCS-FLAG were introduced by the QuickChange site-directed mutagenesis method (Stratagene, primer sequences indicated in supplemental Table 2). pEBB-CCS-GST deletion constructs were kindly obtained from Dr. C. Duckett (Ann Arbor, MI) and described previously (36). A pSUPER-RETRO vector encoding short hairpin RNAs (shRNAs) against COMMD1 (shCOMMD1) was described previously (15,18).…”

Section: Methodsmentioning

confidence: 99%

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Cu,Zn Superoxide Dismutase Maturation and Activity Are Regulated by COMMD1

Vonk

Wijmenga

Berger

et al. 2010

Journal of Biological Chemistry

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The maturation and activation of the anti-oxidant Cu,Zn superoxide dismutase (SOD1) are highly regulated processes that require several post-translational modifications. The maturation of SOD1 is initiated by incorporation of zinc and copper ions followed by disulfide oxidation leading to the formation of enzymatically active homodimers. Our present data indicate that homodimer formation is a regulated final step in SOD1 maturation and implicate the recently characterized copper homeostasis protein COMMD1 in this process. COMMD1 interacts with SOD1, and this interaction requires CCS-mediated copper incorporation into SOD1. COMMD1 does not regulate disulfide oxidation of SOD1 but reduces the level of SOD1 homodimers. RNAi-mediated knockdown of COMMD1 expression results in a significant induction of SOD1 activity and a consequent decrease in superoxide anion concentrations, whereas overexpression of COMMD1 exerts exactly the opposite effects. Here, we identify COMMD1 as a novel protein regulating SOD1 activation and associate COMMD1 function with the production of free radicals.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Cu,Zn Superoxide Dismutase Maturation and Activity Are Regulated by COMMD1

Vonk

Wijmenga

Berger

et al. 2010

Journal of Biological Chemistry

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“…It is unclear how SOD1 is able to influence survival pathways in lung cancer cell lines to permit growth. Recently, it was shown that the antiapoptotic protein XIAP (X-linked inhibitor of apoptosis) can activate SOD1 by ubiquitinating and activating the copper chaperone for superoxide dismutase (CCS), which delivers copper to SOD1, thereby enhancing its enzymatic function (17). It remains to be determined whether a similar process occurs in cancer cells, because the XIAP study was done in mammalian cell lines that were not derived from tumors.…”

Section: Discussionmentioning

confidence: 99%

Superoxide dismutase 1 (SOD1) is a target for a small molecule identified in a screen for inhibitors of the growth of lung adenocarcinoma cell lines

Somwar

Erdjument‐Bromage²,

Larsson³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

140

128

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We previously described four small molecules that reduced the growth of lung adenocarcinoma cell lines with either epidermal growth factor receptor (EGFR) or KRAS mutations in a highthroughout chemical screen. By combining affinity proteomics and gene expression analysis, we now propose superoxide dismutase 1 (SOD1) as the most likely target of one of these small molecules, referred to as lung cancer screen 1 (LCS-1). siRNAs against SOD1 slowed the growth of LCS-1 sensitive cell lines; conversely, expression of a SOD1 cDNA increased proliferation of H358 cells and reduced sensitivity of these cells to LCS-1. In addition, SOD1 enzymatic activity was inhibited in vitro by LCS-1 and two closely related analogs. These results suggest that SOD1 is an LCS-1-binding protein that may act in concert with mutant proteins, such as EGFR and KRAS, to promote cell growth, providing a therapeutic target for compounds like LCS-1.

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“…Protein Identification by Tandem LC/MS-MS-Standard protocols for in-gel digestion followed by mass spectrometry were carried out as described (39). The lanes were excised into 14 equal sized slices and destained with 30% methanol for 4 h. After reduction (10 mM DTT) and alklylation (65 mM iodoacetamide) of the cysteines at room temperature for 30 min, proteins were digested overnight with trypsin (Promega).…”

Section: Methodsmentioning

confidence: 99%

Ordered Assembly of Heat Shock Proteins, Hsp26, Hsp70, Hsp90, and Hsp104, on Expanded Polyglutamine Fragments Revealed by Chemical Probes

Walter

Smith

Wisén

et al. 2011

Journal of Biological Chemistry

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In Saccharomyces cerevisae, expanded polyglutamine (polyQ) fragments are assembled into discrete cytosolic aggregates in a process regulated by the molecular chaperones Hsp26, Hsp70, Hsp90, and Hsp104. To better understand how the different chaperones might cooperate during polyQ aggregation, we used sequential immunoprecipitations and mass spectrometry to identify proteins associated with either soluble (Q25) or aggregation-prone (Q103) fragments at both early and later times after induction of their expression. We found that Hsp26, Hsp70, Hsp90, and other chaperones interact with Q103, but not Q25, within the first 2 h. Further, Hsp70 and Hsp90 appear to be partially released from Q103 prior to the maturation of the aggregates and before the recruitment of Hsp104. To test the importance of this seemingly ordered process, we used a chemical probe to artificially enhance Hsp70 binding to Q103. This treatment retained both Hsp70 and Hsp90 on the polyQ fragment and, interestingly, limited subsequent exchange for Hsp26 and Hsp104, resulting in incomplete aggregation. Together, these results suggest that partial release of Hsp70 may be an essential step in the continued processing of expanded polyQ fragments in yeast.The heat shock proteins (HSPs) 3 are abundant molecular chaperones that have been shown to be important for maintaining proteostasis under both normal conditions and during times of cellular stress (1-3). Together, these factors play multiple roles in quality control, especially related to polypeptide synthesis, folding, and turnover (4 -7). Moreover, HSPs are emerging as drug targets in cancer, neurodegenerative disorders and other diseases (8, 9). Thus, there is interest in better understanding how they coordinate protein quality control decisions.The major families of HSPs are named based on their approximate kDa molecular weights, including Hsp60, Hsp70, Hsp90,

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Regulation of the Copper Chaperone CCS by XIAP-Mediated Ubiquitination

Cited by 66 publications

References 70 publications

Cu,Zn Superoxide Dismutase Maturation and Activity Are Regulated by COMMD1

Cu,Zn Superoxide Dismutase Maturation and Activity Are Regulated by COMMD1

Superoxide dismutase 1 (SOD1) is a target for a small molecule identified in a screen for inhibitors of the growth of lung adenocarcinoma cell lines

Ordered Assembly of Heat Shock Proteins, Hsp26, Hsp70, Hsp90, and Hsp104, on Expanded Polyglutamine Fragments Revealed by Chemical Probes

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