UBQLNs (ubiquilins) are highly conserved proteins across species, characterized by interactions with proteasomes and ubiquitinated proteins via UBA and UBL domains, respectively. The role of UBQLNs as chaperone proteins of the ubiquitin-proteasome system (UPS) is well-defined; however, the connections between UBQLNs and autophagy remain unclear. A recent study published in from Dr. Hugo J. Bellen's lab showed a novel role of UBQLNs in macroautophagy/autophagy regulation through v-ATPase-MTOR signaling using and mammalian neuronal cells. Notably, the highlighted article also investigated the autophagy phenotype of a common amyotrophic lateral sclerosis (ALS)-associated mutation in the gene encoding UBQLN2, demonstrating the contribution of abnormal v-ATPase-MTOR-mediated autophagy in ALS pathogenesis.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984483PMC
http://dx.doi.org/10.1080/15548627.2019.1665293DOI Listing

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Article Synopsis
  • The study investigates how UBQLN2, a protein involved in quality control, affects tau protein levels in neurodegenerative diseases characterized by tau accumulation.* -
  • UBQLN2 was found to lower normal tau levels but its imbalance worsened tau pathology and toxicity in a mouse model of tauopathy.* -
  • The research highlights the importance of maintaining proper UBQLN2 levels for tau homeostasis, suggesting that disruptions in this balance can contribute to neurodegeneration.*
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Ubiquilin Networking in Cancers.

Cancers (Basel)

June 2020

Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Muang, Chiang Mai 50200, Thailand.

Ubiquilins or UBQLNs, members of the ubiquitin-like and ubiquitin-associated domain (UBL-UBA) protein family, serve as adaptors to coordinate the degradation of specific substrates via both proteasome and autophagy pathways. The UBQLN substrates reveal great diversity and impact a wide range of cellular functions. For decades, researchers have been attempting to uncover a puzzle and understand the role of UBQLNs in human cancers, particularly in the modulation of oncogene's stability and nucleotide excision repair.

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UBQLNs (ubiquilins) are highly conserved proteins across species, characterized by interactions with proteasomes and ubiquitinated proteins via UBA and UBL domains, respectively. The role of UBQLNs as chaperone proteins of the ubiquitin-proteasome system (UPS) is well-defined; however, the connections between UBQLNs and autophagy remain unclear. A recent study published in from Dr.

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Ubiquilins (Ubqlns) are a family of ubiquitin receptors that promote the delivery of hydrophobic and aggregated ubiquitinated proteins to the proteasome for degradation. We carried out a proteomic analysis of a B cell lymphoma-derived cell line, BJAB, that requires UBQLN1 for survival to identify UBQLN1 client proteins. When UBQLN1 expression was acutely inhibited, 120 mitochondrial proteins were enriched in the cytoplasm, suggesting that the accumulation of mitochondrial client proteins in the absence of UBQLN1 is cytostatic.

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Ubiquilin4 is an adaptor protein that recruits Ubiquilin1 to the autophagy machinery.

EMBO Rep

April 2013

Department of Infectious Disease, South San Francisco, CA 94080, USA.

Ubiquilins (Ubqlns)-a family of ubiquitin-binding proteins-are involved in several protein degradation pathways and have been implicated in various neurodegenerative diseases. Ubqln1 regulates autophagosome maturation during autophagy-mediated degradation. We now show that Ubqln4 mediates the interaction between Ubqln1 and the autophagy machinery by recruiting Ubqln1 to LC3.

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