The ubiquitinated and aggregated proteins or cytoplasmic inclusions in degenerating motor neurons is a pathological hallmark of ALS.  UBQLN2 facilitates ubiquitinated protein clearance and its mutations have been linked to ALS. However, the regulation of UBQLN2 is poorly understood. We previously identified HuR as a key regulator of TDP-43 and FUS through posttranscriptional mechanism. The posttranscriptional regulation of UBQLN2 by HuR may play a role in aberrant accumulation and dysfunction of a network of RNA binding proteins associated with ALS.

UBQLN2 expression was analyzed by Western blot after HuR was upregulated ectopically or knocked down in U251 cells by siRNA.  A proteasomal marker d2EGFP was used to access the integrity of ubiquitin-proteasome pathway and downstream function of UBQLN2.  RNA expression levels were measured by qRT-PCR. Subcellular localization and aggregate formation was analyzed by fluorescence immunocytochemistry. Protein stability was analyzed by Cycloheximide chase assay.