The Enigma of Tripeptidyl-Peptidase II: Dual Roles in Housekeeping and Stress

Table 1

Phenotypes/pathways influenced by altered expression of selected cytosolic peptidase𝑠^&.

Pathway/phenomena^#	Model	Ref.
Tripeptidyl-peptidase II (TPPII)
Neuropeptide degradation	cells	[2]
MHC class I processing*	cells	[15–21, 25–28]
	KO/GTmice	[18, 27]
Muscle wasting/cachexia	rats	[29, 30]
Resistance to proteasome inh.*	cells	[11–14, 31]
Apoptosis progression*	cells	[25]
DNA damage response*	cells	[32, 33]
G2/M progression	cells	[34, 35]
Fat formation	KO (+/−) mice	[36]
Hematopoietic homeostasis*	KO/GT mice	[27, 37]
Organismal lifespan	KO mice	[37]
Thimet Oligopeptidase (TOP)
Neuropeptide degradation	cells	[22]
APP processing^⋆	cells	[38]
MHC class I processing	cells	[39]
Bleomycin Hydrolase
APP processing^⋆	cells	[40]
MHC class I processing*	cells	[41]
Bleomycin resistance	KO mice	[42]
Dermal maturation	KO mice	[42]
Astrogliosis	KO mice	[43]
Cognitive functions	KO mice	[43]
Homocysteine metabolism	cells	[44]
Puromycin-sensitive aminopeptidase
(PSA)
MHC class I processing*	cells/KO mice	[45]
G2/M progression	cells	[46]
Growth, reproduction	KO/GT mice	[47]
Anxiety, pain control	GT mice	[47]

^&Phenotypes and pathways studied in live mammalian cells or in mice.
^#Both known pathways and phenomena, several of unknown cause, are included in this list. Thereby, it is possible that some phenomena are the result of some of the known pathways, although the link has not been made. For example, it is unclear whether degradation of neuropeptides contributes to any of the signs in TPPII−/− mice.
^∗The contribution of the peptidase is debated, since reports show both a presence and absence of a role in the phenomenon.
^@KO: knock-out mice; GT gene-trapped mice.
^⋆𝐴PP: amyloid precursor protein.