Proteasomes get by with lots of help from their friends.

Proteasomes can't do it all. It was previously known that aminopeptidases frequently degrade proteasome-generated peptides. Now it appears that another protease, tripeptidyl peptidase II (TPP II), plays a critical role in cleaving proteasomal produced peptides into shorter peptides that can then be degraded by aminopeptidases.

[1]  A. Goldberg,et al.  The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8–9 residues , 2002, Nature Immunology.

[2]  M. Bogyo,et al.  A proteolytic system that compensates for loss of proteasome function , 1998, Nature.

[3]  Kees Jalink,et al.  Peptide diffusion, protection, and degradation in nuclear and cytoplasmic compartments before antigen presentation by MHC class I. , 2003, Immunity.

[4]  N. Shastri,et al.  Producing nature's gene-chips: the generation of peptides for display by MHC class I molecules. , 2002, Annual review of immunology.

[5]  N. Shastri,et al.  ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum , 2002, Nature.

[6]  J. Yewdell,et al.  Cells adapted to the proteasome inhibitor 4-hydroxy- 5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone require enzymatically active proteasomes for continued survival. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Jacques Neefjes,et al.  A major role for TPPII in trimming proteasomal degradation products for MHC class I antigen presentation. , 2004, Immunity.

[8]  W. Baumeister,et al.  A giant protease with potential to substitute for some functions of the proteasome. , 1999, Science.

[9]  A. Goldberg,et al.  Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules , 1994, Cell.

[10]  J. Yewdell,et al.  Making sense of mass destruction: quantitating MHC class I antigen presentation , 2003, Nature Reviews Immunology.

[11]  Concepción Marañón,et al.  An essential role for tripeptidyl peptidase in the generation of an MHC class I epitope , 2003, Nature Immunology.