Tripeptidyl peptidase II in haemolysates and liver homogenates of various species

Bålöw, R M; Eriksson, Inger

doi:10.1042/bj2410075

Cited by 30 publications

(3 citation statements)

References 20 publications

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“…The assembled enzyme functions as an exopeptidase that removes tripeptides from the free N-terminus of polypeptides (Balow and Eriksson, 1987; Balow et al 1983; Balow et al 1986; Tomkinson et al 1997), but also exhibits endopeptidase activity towards long peptides (Geier et al 1999; Seifert et al 2003). We have previously demonstrated that overexpression of TPPII in Burkitt’s lymphoma or transfected HEK293 cells correlates with accelerated proliferation and with the accumulation of centrosome and chromosome aberrations, whereas functional knockdown of TPPII by shRNA results in growth retardation and the accumulation of polynucleated cells that fail to complete cell division (Stavropoulou et al 2005).…”

Section: Introductionmentioning

confidence: 99%

The MAPK Signaling Cascade is a Central Hub in the Regulation of Cell Cycle, Apoptosis and Cytoskeleton Remodeling by Tripeptidyl-Peptidase II

Sompallae

Stavropoulou

Houde

et al. 2008

Gene�Regul Syst Bio

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Tripeptidyl-peptidase II (TPPII) is a serine peptidase highly expressed in malignant Burkitt’s lymphoma cells (BL). We have previously shown that overexpression of TPPII correlates with chromosomal instability, centrosomal and mitotic spindle abnormalities and resistance to apoptosis induced by spindle poisons. Furthermore, TPPII knockdown by RNAi was associated with endoreplication and the accumulation of polynucleated cells that failed to complete cell division, indicating a role of TPPII in the cell cycle. Here we have applied a global approach of gene expression analysis to gain insights on the mechanism by which TPPII regulates this phenotype. mRNA profiling of control and TPPII knockdown BL cells identified one hundred and eighty five differentially expressed genes. Functional categorization of these genes highlighted major physiological functions such as apoptosis, cell cycle progression, cytoskeleton remodeling, proteolysis, and signal transduction. Pathways and protein interactome analysis revealed a significant enrichment in components of MAP kinases signaling. These findings suggest that TPPII influences a wide network of signaling pathways that are regulated by MAPKs and exerts thereby a pleiotropic effect on biological processes associated with cell survival, proliferation and genomic instability.

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Section: Introductionmentioning

confidence: 99%

The MAPK Signaling Cascade is a Central Hub in the Regulation of Cell Cycle, Apoptosis and Cytoskeleton Remodeling by Tripeptidyl-Peptidase II

Sompallae

Stavropoulou

Houde

et al. 2008

Gene�Regul Syst Bio

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“…Tripeptidyl‐peptidase II (TPP II) (EC 3.4.14.10) is an enzyme with remarkable characteristics. It was discovered 1983 as an extralysosomal peptidase in rat liver [1] and has since been extensively characterized [2–6]. It is one of only two known mammalian tripeptide‐releasing enzymes (reviewed in [7]).…”

mentioning

confidence: 99%

The insert within the catalytic domain of tripeptidyl‐peptidase II is important for the formation of the active complex

Tomkinson

Laoi

Wellington

2002

European Journal of Biochemistry

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Tripeptidyl-peptidase II (TPP II) is a large (M r >10 6 ) tripeptide-releasing enzyme with an active site of the subtilisin-type. Compared with other subtilases, TPP II has a 200 amino-acid insertion between the catalytic Asp44 and His264 residues, and is active as an oligomeric complex. This study demonstrates that the insert is important for the formation of the active high-molecular mass complex. A recombinant human TPP II and a murine TPP II were found to display different complex-forming characteristics when over-expressed in human 293-cells; the human enzyme was mainly in a nonassociated, inactive state whereas the murine enzyme formed active oligomers. This was surprising because native human TPP II is purified from erythrocytes as an active oligomeric complex, and the amino-acid sequences of the human and murine enzymes were 96% identical. Using a combination of chimeras and a single point mutant, the amino acid responsible for this difference was identified as Arg252 in the recombinant human sequence, which corresponds to a glycine in the murine sequence. As Gly252 is conserved in all sequenced variants of TPP II, the recombinant enzyme with Arg252 is atypical. Nevertheless, as Arg252 evidently interferes with complex formation, and this residue is close to the catalytic His264, it may also explain why oligomerization influences enzyme activity. The exact mechanism for how the G252R substitution interferes with complex formation remains to be determined, but will be of importance for the understanding of the unique properties of TPP II.

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“…Both fragments are biologically inactive. The discovery of tripeptidyl peptidase II in rat liver cytosol was first reported in 1983 and the enzyme has been extensively characterized since then [6][7][8][9]. It is an extralysosomal serine peptidase with an active site of the subtilisin type.…”

Section: Introductionmentioning

confidence: 99%

Inhibitor-based validation of a homology model of the active-site of tripeptidyl peptidase II

Winter¹,

Breslin²,

Miskowski³

et al. 2005

Journal of Molecular Graphics and Modelling

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Tripeptidyl peptidase II in haemolysates and liver homogenates of various species

Cited by 30 publications

References 20 publications

The MAPK Signaling Cascade is a Central Hub in the Regulation of Cell Cycle, Apoptosis and Cytoskeleton Remodeling by Tripeptidyl-Peptidase II

The MAPK Signaling Cascade is a Central Hub in the Regulation of Cell Cycle, Apoptosis and Cytoskeleton Remodeling by Tripeptidyl-Peptidase II

The insert within the catalytic domain of tripeptidyl‐peptidase II is important for the formation of the active complex

Inhibitor-based validation of a homology model of the active-site of tripeptidyl peptidase II

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