Antigen Processing and Presentation by MHC Class I, II, and Nonclassical Molecules

The proteasome regulator PSME4 drives immune evasion and abrogates anti-tumor immunity in NSCLC

“…In addition to the core particle of the proteasome ,proteasome composition and the degradation landscape may be affected by specific regulatory particles such as the 19S regulatory complex (PSMC1-6 and PSMD1-14), or the regulatory caps PA28αβ (PSME1-2), PA28γ (PSME3) or PA200 (PSME4) (Collins and Goldberg, 2017;Coux et al, 2020;Rousseau and Bertolotti, 2018) that bind the catalytic core and affect gate opening and substrate selection. The 19S regulatory complex been shown to be pivotal for binding of ubiquitinated species and substrate unfolding, while the other regulatory subunits are suggested to have more specialized roles, including mediating inflammatory responses, histone degradation, and the response to DNA damage (Antoniou et al, 2012;Blickwedehl et al, 2012;Collins and Goldberg, 2017;Khor et al, 2006;Mandemaker et al, 2018aMandemaker et al, , 2018bQian et al, 2013;Rousseau and Bertolotti, 2018;Ustrell et al, 2002;Welk et al, 2016). The different catalytic cores, together with the diverse range of regulatory subunits, introduce great potential diversity for generating hybrid proteasomes of the 20S core particle with different combinations of regulatory caps, thereby altering protein cleavage (Fabre et al, 2014(Fabre et al, , 2015Morozov and Karpov, 2019;Raule et al, 2014;Toste Rêgo and da Fonseca, 2019).…”