Prothymosin-α Interacts with Mutant Huntingtin and Suppresses Its Cytotoxicity in Cell Culture

Dong, Gaofeng; Callegari, Eduardo; Gloeckner, Christian Johannes; Ueffing, Marius; Wang, Hongmin

doi:10.1074/jbc.m111.294280

Cited by 27 publications

(32 citation statements)

References 31 publications

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“…Cell lysates or isolated protein aggregates were sonicated and then separated in 12% SDS PAGE before transferred onto a nitrocellulose membrane for immunoblotting analysis as previously described (Dong et al 2012). The primary and secondary antibodies were previously described (Liu et al 2014a).…”

Section: Methodsmentioning

confidence: 99%

Enhanced Proteostasis in Post-ischemic Stroke Mouse Brains by Ubiquilin-1 Promotes Functional Recovery

Qiao

Wang

2016

Cell Mol Neurobiol

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Stroke is pathologically associated with oxidative stress, protein damage, and neuronal loss. We previously reported that overexpression of a ubiquitin-like protein, ubiquilin-1 (Ubqln), protects neurons against ischemia-caused brain injury, while knockout of the gene exacerbates cerebral ischemia-caused neuronal damage and delays functional recovery. Although these observations indicate that Ubqln is a potential therapeutic target, transgenic manipulation-caused overexpression of Ubqln occurs before the event of ischemic stroke, and it remains unknown whether delayed Ubqln overexpression in post-ischemic brains within a clinically relevant time frame is still beneficial. To address this question, we generated lentiviruses either overexpressing or knocking down mouse Ubqln, and treated post-ischemic stroke mice 6 h following the middle cerebral artery occlusion with the lentiviruses before animal behaviors were evaluated at day 1, 3, 5, and 7. Our data indicate that post-ischemic overexpression of Ubqln significantly promoted functional recovery, whereas post-ischemic downregulation of Ubqln expression delays functional recovery. To further understand the mechanisms underlying how Ubqln functions, we also isolated protein aggregates from the brains of wild-type mice or the mice overexpressing Ubqln following ischemia/reperfusion. Western blot analysis indicates that overexpression of Ubqln significantly reduced the accumulation of protein aggregates. These observations not only suggest that Ubqln is a useful candidate for therapeutic intervention for ischemic stroke but also highlight the significance of proteostasis in functional recovery following stroke.

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Section: Methodsmentioning

confidence: 99%

Enhanced Proteostasis in Post-ischemic Stroke Mouse Brains by Ubiquilin-1 Promotes Functional Recovery

Qiao

Wang

2016

Cell Mol Neurobiol

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“…7), it is thought that reduced prefoldin activity is directly associated with pathogenic HTT-induced cell toxicity. It has recently been reported that prothymosin-␣ interacted with pathogenic HTT and suppressed its toxicity through inhibiting pathogenic HTT-induced apoptosis pathway (56). Prothymosin-␣ was co-localized with HTT in the nucleus and facilitated aggregate formation of pathogenic HTT (56).…”

Section: ϫ5mentioning

confidence: 97%

“…It has recently been reported that prothymosin-␣ interacted with pathogenic HTT and suppressed its toxicity through inhibiting pathogenic HTT-induced apoptosis pathway (56). Prothymosin-␣ was co-localized with HTT in the nucleus and facilitated aggregate formation of pathogenic HTT (56). Although both prefoldin and prothymosin-␣ show protective activity against the toxicity of pathogenic HTT, their mechanisms may be different.…”

Section: ϫ5mentioning

confidence: 99%

Prefoldin Protects Neuronal Cells from Polyglutamine Toxicity by Preventing Aggregation Formation

Tashiro

Zako

Muto

et al. 2013

Journal of Biological Chemistry

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Background: Prefoldin, a molecular chaperone composed of six subunits, prevents misfolding of newly synthesized nascent polypeptides. Results: Prefoldin inhibited aggregation of pathogenic Huntingtin and subsequent cell death. Conclusion: Prefoldin suppressed Huntingtin aggregation at the small oligomer stage. Significance: Prefoldin plays a role in preventing protein aggregation in Huntington disease.

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“…The supernatant was used for Western blot analysis. Protein concentration in the supernatant was determined using the BCA assay kit (Pierce) and the procedure for the Western blot was described previously (Dong et al 2012). The primary antibodies used in the studies include the antibodies against proteasomal 20S b1i (LMP2) (Enzo, 1:2,000), 20S b2i (MECL1) (Enzo, 1:2,000), 20S b5i (LMP7) (Enzo, 1:2,000), ubiquitin (Enzo, 1:2,000), and b-tubulin (Cell Signaling, 1:5,000).…”

Section: Western Blot Analysismentioning

confidence: 99%

Transient Focal Cerebral Ischemia Upregulates Immunoproteasomal Subunits

Lü

Wang

2012

Cell Mol Neurobiol

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This study was designed to determine whether focal cerebral ischemia alters the expression of the immunoproteasomal (i-proteasomal) subunits. Transient cerebral ischemia significantly increased the expression of the i-proteasomal subunits, 20S β1i (LMP2) and β5i (LMP7) in the parietal cortex and hippocampus. This alteration was associated with a remarkable increase in ubiquitinated proteins. It is likely that the postischemic induction of the i-proteasome plays an important role in coping with the damaged proteins and thus may have an important effect on neuronal survival and death.

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Prothymosin-α Interacts with Mutant Huntingtin and Suppresses Its Cytotoxicity in Cell Culture

Cited by 27 publications

References 31 publications

Enhanced Proteostasis in Post-ischemic Stroke Mouse Brains by Ubiquilin-1 Promotes Functional Recovery

Enhanced Proteostasis in Post-ischemic Stroke Mouse Brains by Ubiquilin-1 Promotes Functional Recovery

Prefoldin Protects Neuronal Cells from Polyglutamine Toxicity by Preventing Aggregation Formation

Transient Focal Cerebral Ischemia Upregulates Immunoproteasomal Subunits

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