TY - JOUR
T1 - The functional and mechanistic roles of immunoproteasome subunits in cancer
AU - Tripathi, Satyendra Chandra
AU - Vedpathak, Disha
AU - Ostrin, Edwin Justin
N1 - Funding Information:
The authors would like to thank the Lung Cancer Research Foundation and the University of Texas MD Anderson Physician Scientist Program for support. S.C.T would like to acknowledge SERB-DST for providing the startup research grant SERB-DST-SRG/2020/001564.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12
Y1 - 2021/12
N2 - Cell-mediated immunity is driven by antigenic peptide presentation on major histocompat-ibility complex (MHC) molecules. Specialized proteasome complexes called immunoproteasomes process viral, bacterial, and tumor antigens for presentation on MHC class I molecules, which can induce CD8 T cells to mount effective immune responses. Immunoproteasomes are distinguished by three subunits that alter the catalytic activity of the proteasome and are inducible by inflammatory stimuli such as interferon-γ (IFN-γ). This inducible activity places them in central roles in cancer, autoimmunity, and inflammation. While accelerated proteasomal degradation is an important tu-morigenic mechanism deployed by several cancers, there is some ambiguity regarding the role of immunoproteasome induction in neoplastic transformation. Understanding the mechanistic and functional relevance of the immunoproteasome provides essential insights into developing targeted therapies, including overcoming resistance to standard proteasome inhibition and immunomodula-tion of the tumor microenvironment. In this review, we discuss the roles of the immunoproteasome in different cancers.
AB - Cell-mediated immunity is driven by antigenic peptide presentation on major histocompat-ibility complex (MHC) molecules. Specialized proteasome complexes called immunoproteasomes process viral, bacterial, and tumor antigens for presentation on MHC class I molecules, which can induce CD8 T cells to mount effective immune responses. Immunoproteasomes are distinguished by three subunits that alter the catalytic activity of the proteasome and are inducible by inflammatory stimuli such as interferon-γ (IFN-γ). This inducible activity places them in central roles in cancer, autoimmunity, and inflammation. While accelerated proteasomal degradation is an important tu-morigenic mechanism deployed by several cancers, there is some ambiguity regarding the role of immunoproteasome induction in neoplastic transformation. Understanding the mechanistic and functional relevance of the immunoproteasome provides essential insights into developing targeted therapies, including overcoming resistance to standard proteasome inhibition and immunomodula-tion of the tumor microenvironment. In this review, we discuss the roles of the immunoproteasome in different cancers.
KW - Immunoproteasome
KW - Proteasome inhibitors
KW - Solid tumors
KW - Ubiquitin–proteasome system (UPS)
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U2 - 10.3390/cells10123587
DO - 10.3390/cells10123587
M3 - Review article
C2 - 34944095
AN - SCOPUS:85121389014
SN - 2073-4409
VL - 10
JO - Cells
JF - Cells
IS - 12
M1 - 3587
ER -