Proteasome 20S Subunit Beta 8 gene

The PSMB8 gene (PSMB8 stands for: proteasome 20S subunit beta 8) is a protein coding gene located on chromosome 6p21.32. Two alternative transcripts encoding two isoforms have been identified; both isoforms are processed to produce the same mature subunit.

The proteasome is a multicatalytic proteinase complex characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu and Glu next to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB5 with PSMB8 increases the ability of the immunoproteasome to cleave model peptides after hydrophobic and basic residues.

The coding protein is involved in the formation of spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parent protein (Ebstein F et al. 2016). Acts as a major component of interferon-gamma-induced susceptibility. Plays a key role in apoptosis by degrading the apoptosis inhibitor MCL1. In cancer cells, the substitution of isoform 1 (E2) by isoform 2 (E1) leads to a lack of immunoproteasomes. Required for the differentiation of preadipocytes into adipocytes.

Diseases associated with PSMB8 include

proteasome-associated auto-inflammatory syndrome 1

and

Nakajo syndrome.

1. Ebstein F et al. (2016) Proteasomes generate spliced epitopes by two different mechanisms and as efficiently as non-spliced epitopes. Sci Rep 6:24032.