The ubiquitin-proteasome system and chromosome 17 in cerebellar granule cells and medulloblastoma subgroups

Abstract

Chromosome 17 abnormalities are often observed in medulloblastomas (MBs), particularly those classified in the consensus Groups 3 and 4. Herein we review MB signature genes associated with chromosome 17 and the relationship of these signature genes to the ubiquitin-proteasome system. While clinical investigators have not focused on the ubiquitin-proteasome system in relation to MB, a substantial amount of data on the topic has been hidden in the form of supplemental datasets of gene expression. A supplemental dataset associated with the Thompson classification of MBs shows that a subgroup of MB with 17p deletions is characterized by reduced expression of genes for several core particle subunits of the beta ring of the proteasome (β1, β4, β5, β7). One of these genes (PSMB6, the gene for the β1 subunit) is located on chromosome 17, near the telomeric end of 17p. By comparison, in the WNT group of MBs only one core proteasome subunit, β6, associated with loss of a gene (PSMB1) on chromosome 6, was down-regulated in this dataset. The MB subgroups with the worst prognosis have a significant association with chromosome 17 abnormalities and irregularities of APC/C cyclosome genes. We conclude that the expression of proteasome subunit genes and genes for ubiquitin ligases can contribute to prognostic classification of MBs. The therapeutic value of targeting proteasome subunits and ubiquitin ligases in the various subgroups of MB remains to be determined separately for each classification of MB.

Transcriptomic analysis identifies shared biological foundations between ischemic stroke and Alzheimer’s disease

“…Wu et al (2022) suggested that RPS3 and RPS15 may be potential targets and treatment for early diagnosis of AIS. PSMB6, also known as 20S proteasome subunit beta-1, codes for the β1 core catalytic subunit of the proteasome (Vriend and Marzban, 2017). A study showed that PSMB6 was a critical regulator of circadian rhythm, which may also have a direct or indirect effect on neurodegenerative diseases (Beker and KiliÇ, 2020).…”

The role of circadian rhythm in the regulation of cellular protein profiles in the brain

“…In addition, it is predicted that SRC is a non-receptor tyrosine kinase that plays an important role in the Parkinson's disease which is the second most common neurodegenerative disorders after Alzheimer's disease [29]. PSMB6 also known as 20S proteasome subunit beta-1 which codes for the β1 core catalytic subunit of the proteasome [30]. RL10 is one of large ribosomal proteins and plays an important role in cell proliferation, migration and differentiation [31].…”