Peter Wujek

TL;DR: A dual role of oligosaccharide at Asn-286 in folding and lysosomal targeting could contribute to the unusual, but cell type-dependent, fate of misfolded TPP I conformer and represent the molecular basis of the disease process in subjects with naturally occurring missense mutation.

TL;DR: Analysis of the effect of various classes of protease inhibitors and mutation of the active site Ser475 on human TPP I maturation in cultured cells demonstrated that although TPP I zymogen is capable of autoactivation in vitro, a serine protease that is sensitive to AEBSF participates in processing of the proenzyme to the mature, active form in vivo.

TL;DR: The findings suggest that TPP I is involved in general protein turnover and that its expression may be controlled by various regulatory mechanisms, which highlights the importance of this enzyme for normal function of cells and organs in humans.

TL;DR: The process of maturation in vitro of recombinant latent human TPP I purified to homogeneity from secretions of Chinese hamster ovary cells overexpressing TPP I cDNA is examined to suggest that in vivo mature enzyme does not significantly participate in its own generation from the precursor.

TL;DR: The study shows thatTPP-I is absent or appears in very small amounts not only in cLINCL subjects with mutations producing severely truncated protein, but also in individuals with missense point mutations, which correlates with loss of TPP-I activity, which suggests that TPP- I participates in lysosomal turnover of proteins in pathological conditions associated with cell/tissue injury.