Tripeptidyl peptidase II in human oral squamous cell carcinoma

Usukura, Katsuya; Kasamatsu, Atsushi; Okamoto, Atsushi; Kouzu, Yukinao; Higo, Morihiro; Koike, Hirofumi; Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

doi:10.1007/s00432-012-1307-y

Cited by 25 publications

(20 citation statements)

References 34 publications

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“…3) with mock shRNA. Consistent with literature (12,50), it needs to be mentioned that a higher knock down led to growth arrest and cell death. As a filtering criterion, we only considered proteins that were reproducibly (P1, p Ͻ .05) more than 1.25-fold (significance B, Intensity versus log2FC, p Ͻ .05) (44) increased or decreased as being influenced by TPP2 if they were changed in the same direction in at least two out of the three screens.…”

Section: Proteomic Changes By Tpp2 Inhibition and Knocksupporting

confidence: 82%

“…IC 50 Value and TPP2 Irreversibility-For determination of the IC 50 value, human TPP2 (hsTPP2) was incubated with butabindide (Tocris Biosciences, Bristol, UK) or B6 at concentrations between 5 pM and 1 M in 0.1 M potassium phosphate buffer, pH 7.5, containing 12% glycerol and 2 mM DTT for 15 min at 37°C before addition of 100 M H-Ala-Ala-Phe-pNA (AAF-pNA). The change in absorbance at 405 nm was measured continuously for 45 min (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…3). Neuron differentiation, proliferation, cell differentiation and development, growth factor signaling, learning, DNA damage response, and phosphorylation (Table I) were the main overrepresented biological processes (26,50,53). Importantly, the involvement of TPP2 in neuron differentiation and in learning has not been described before, probably mediated by its influence on the transcription factor SOX11 (54 -56).…”

Section: Proteomic Changes By Tpp2 Inhibition and Knockmentioning

confidence: 97%

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Tripeptidyl Peptidase II Mediates Levels of Nuclear Phosphorylated ERK1 and ERK2

Wiemhoefer

Stargardt

Linden

et al. 2015

Molecular & Cellular Proteomics

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Tripeptidyl peptidase II (TPP2) is a serine peptidase involved in various biological processes, including antigen processing, cell growth, DNA repair, and neuropeptide mediated signaling. The underlying mechanisms of how a peptidase can influence this multitude of processes still remain unknown. We identified rapid proteomic changes in neuroblastoma cells following selective TPP2 inhibition using the known reversible inhibitor butabindide, as well as a new, more potent, and irreversible peptide phosphonate inhibitor. Our data show that TPP2 inhibition indirectly but rapidly decreases the levels of active, di-phosphorylated extracellular signal-regulated kinase 1 (ERK1) and ERK2 in the nucleus, thereby down-regulating signal transduction downstream of growth factors and mitogenic stimuli. We conclude that TPP2 mediates many important cellular functions by controlling ERK1 and ERK2 phosphorylation. For instance, we show that TPP2 inhibition of neurons in the hippocampus leads to an excessive strengthening of synapses, indicating that TPP2 activity is crucial for normal brain function. Molecular & Cellular

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Section: Proteomic Changes By Tpp2 Inhibition and Knocksupporting

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Section: Proteomic Changes By Tpp2 Inhibition and Knockmentioning

confidence: 97%

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Tripeptidyl Peptidase II Mediates Levels of Nuclear Phosphorylated ERK1 and ERK2

Wiemhoefer

Stargardt

Linden

et al. 2015

Molecular & Cellular Proteomics

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“…The transfectants were plated on chamber slides (BD Falcon, Franklin Lakes, NJ) at 50% confluency, washed with ice-cold PBS, and fixed with 4% paraformaldehyde-PBS for 20 minutes, then permeabilized in PBS containing 0.2% Triton X-100 as previously described [43]. We used the following primary antibodies to detect SAC activation: rabbit anti-KIF4A polyclonal antibody (Gene Tex), mouse anti-BUB1 monoclonal antibody (Santa Cruz Biotechnology), and mouse anti-MAD2 antibody (Santa Cruz Biotechnology).…”

Section: Methodsmentioning

confidence: 99%

Kinesin Family member 4A: A Potential Predictor for Progression of Human Oral Cancer

et al. 2013

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BackgroundKinesin family member 4A (KIF4A), a microtubule-based motor protein, was implicated in regulation of chromosomal structure and kinetochore microtubule dynamics. Considering the functions of KIF4A, we assumed that KIF4A is involved in progression of oral squamous cell carcinomas (OSCCs) via activation of the spindle assembly checkpoint (SAC). However, little is known about the relevance of KIF4A in the behavior of OSCC. We investigated the KIF4A expression status and its functional mechanisms in OSCC.MethodsThe KIF4A expression levels in seven OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Using a KIF4A knockdown model, we assessed the expression of (SAC)-related molecules (BUB1, MAD2, CDC20, and cyclin B1), cell-cycle, and cellular proliferation. In addition to in vitro data, the clinical correlation between the KIF4A expression levels in primary OSCCs (n = 106 patients) and the clinicopathologic status by immunohistochemistry (IHC) also were evaluated. ResultsKIF4A mRNA and protein were up-regulated significantly (P < 0.05) in seven OSCC-derived cells compared with human normal oral keratinocytes. In the KIF4A knockdown cells, SAC activation was observed via increased BUB1 expression on the kinetochores, appropriate kinetochore localization of MAD2, down-regulation of CDC20, up-regulation of cyclin B1, and cell-cycle arrested at G2/M phase. The results showed that cellular proliferation of KIF4A knockdown cells decreased significantly (P < 0.05) compared with control cells. IHC showed that KIF4A expression in primary OSCCs was significantly (P < 0.05) greater than in the normal oral counterparts and that KIF4A-positive OSCCs were correlated closely (P < 0.05) with tumoral size. ConclusionsOur results proposed for the first time that KIF4A controls cellular proliferation via SAC activation. Therefore, KIF4A might be a key regulator for tumoral progression in OSCCs.

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“…Abnormal pathological proteins can be degraded independent of the ubiquitin-proteasome system. Tripeptidyl peptidase II (TPP II) has attracted increasing attention as a small peptidic enzyme that degrades macromolecular proteins [10,11]. TPPII has been described in virtually all eukaryotic cells.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus Vector Harboring the HBcAg and Tripeptidyl Peptidase II Genes Induces Potent Cellular Immune Responses In Vivo

Tan¹,

Ma²,

Hu³

et al. 2017

Cell Physiol Biochem

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Background: Chronic hepatitis B virus (HBV) infection is associated with a weak but specific cellular immune response of the host to HBV. Tripeptidyl peptidaseⅡ (TPPⅡ), an intracellular macromolecule and proteolytic enzyme, plays an important complementary and compensatory role for the proteasome during viral protein degradation and major histocompatibility complex class I antigen presentation by inducing a specific cellular immune response in vivo. Based on a previous study, we aimed to explore the role of MHC class I antigen presentation in vivo and the mechanisms that may be involved. Methods: In this study, recombinant adenoviral vectors harboring the hepatitis B core antigen (HBcAg) and the TPPII gene were constructed (Adv-HBcAg and Adv-HBcAg-TPPII), and H-2Kd HBV-transgenic BALB/c mice and HLA-A2 C57BL/6 mice were immunized with these vectors, respectively. We evaluated the specific immune responses induced by Adv-HBcAg-TPPII in the HBV transgenic BALB/c mice and HLA-A2 C57BL/6 mice as well as the anti-viral ability of HBV transgenic mice, and we explored the underlying mechanisms. Results: We found that immunization with Adv-HBcAg-TPPII induced the secretion of the cytokines interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) as well as the activities of IFN-γ-secreting CD8+ T cells and CD4+ T cells. In addition, HBcAg-specific CTL activity in C57/BL mice and HBV transgenic animals was significantly enhanced in the Adv-HBcAg-TPPII group. Furthermore, Adv-HBcAg-TPPII decreased the hepatitis B surface antigen (HBsAg) and HBV DNA levels and the amount of HBsAg and HBcAg in liver tissues. Moreover, Adv-HBcAg-TPPII enhanced the expression of T-box transcription factor (T-bet) and downregulated GATA-binding protein 3 (GATA-3) while increasing the expression levels of JAK2, STAT1, STAT4 and Tyk2. Conclusions: These results suggested that the JAK/STAT signaling pathway participates in the CTL response that is mediated by the adenoviral vector encoding TPPII. Adv-HBcAg-TPPII could therefore break immune tolerance and stimulate HBV-specific cytotoxic T lymphocyte activity and could have a good therapeutic effect in transgenic mice.

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Tripeptidyl peptidase II in human oral squamous cell carcinoma

Abstract: The current study showed that overexpression of TPP2 occurs frequently during oral carcinogenesis and might be associated with OSCC progression via SAC activation.

Cited by 25 publications

References 34 publications

Tripeptidyl Peptidase II Mediates Levels of Nuclear Phosphorylated ERK1 and ERK2

Tripeptidyl Peptidase II Mediates Levels of Nuclear Phosphorylated ERK1 and ERK2

Kinesin Family member 4A: A Potential Predictor for Progression of Human Oral Cancer

Adenovirus Vector Harboring the HBcAg and Tripeptidyl Peptidase II Genes Induces Potent Cellular Immune Responses In Vivo

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