Testisin, a Glycosyl-Phosphatidylinositol–Linked Serine Protease, Promotes Malignant Transformation <i>In vitro</i> and <i>In vivo</i>

Tang, Tenny; Kmet, Muriel; Corral, Laura G.; Vartanian, Steffan; Tobler, Andreas; Papkoff, Jackie

doi:10.1158/0008-5472.868.65.3

Cited by 33 publications

(4 citation statements)

References 40 publications

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“…The lack of two of the six WD repeats in the identified N-acetylated isoform will likely affect the ability of the protein to form the propeller. Another example is the serine protease testisin, a tumor suppressor of testicular cancer that is highly abundant in ovarian cancer , . The active site of testisin consists of a charge relay system composed of the residues His82, Asp137, and Ser238 .…”

Section: Resultsmentioning

confidence: 99%

“…Another example is the serine protease testisin, a tumor suppressor of testicular cancer that is highly abundant in ovarian cancer. 43,44 The active site of testisin consists of a charge relay system composed of the residues His82, Asp137, and Ser238. 45 We identified an isoform starting with N-acetyl-DIALVK at residue 137, which is the second of these critical residues (Figure 3b).…”

Section: T H I S C O N T E N T Imentioning

confidence: 99%

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Targeted Analysis of Protein Termini

et al. 2007

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We describe a targeted analysis of protein isoforms by selective enrichment and identification of in vivo acetylated protein N-termini and protein C-termini. Our method allows the characterization of these protein termini regardless of their annotation in protein databases and requires no chemical derivatization. Using an iterative database search strategy that takes account of the enrichment protocol, 263 IPI annotated and 87 unpredicted acetylated N-termini were identified in the crude membrane fraction of human embryonic carcinoma cells. The N-acetylated peptides conform to the reported criteria for in vivo modification. In addition, 168 IPI annotated and 193 unpredicted C-termini were identified. Additionally, and for the first time, we also report on in vivo N-terminal propionylation. The significant number of unknown protein N-and C-termini suggests a high degree of novel transcription independent of annotated gene boundaries and/or specific protein processing. Biological relevance of several of these unpredicted protein termini could be curated from the literature, adding further weight to the argument to go beyond routine database search strategies. Our method will improve the correct annotation of genes and proteins in databases.

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Section: Resultsmentioning

confidence: 99%

Section: T H I S C O N T E N T Imentioning

confidence: 99%

Targeted Analysis of Protein Termini

et al. 2007

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“…Testisin is a glycosyl-phosphatidylinositol-linked serine protease that is encoded by PRSS21. In soft agar, silencing endogenous testis in mRNA results in increased apoptosis and decreased growth [53]. The TRGs identified in this study may play a role in carcinogenesis and require further investigation.…”

Section: Discussionmentioning

confidence: 78%

Epigenetic and Tumor Microenvironment for Prognosis of Patients with Gastric Cancer

Zhang

Fan

et al. 2023

Biomolecules

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Background: Epigenetics studies heritable or inheritable mechanisms that regulate gene expression rather than altering the DNA sequence. However, no research has investigated the link between TME-related genes (TRGs) and epigenetic-related genes (ERGs) in GC. Methods: A complete review of genomic data was performed to investigate the relationship between the epigenesis tumor microenvironment (TME) and machine learning algorithms in GC. Results: Firstly, TME-related differential expression of genes (DEGs) performed non-negative matrix factorization (NMF) clustering analysis and determined two clusters (C1 and C2). Then, Kaplan–Meier curves for overall survival (OS) and progression-free survival (PFS) rates suggested that cluster C1 predicted a poorer prognosis. The Cox–LASSO regression analysis identified eight hub genes (SRMS, MET, OLFML2B, KIF24, CLDN9, RNF43, NETO2, and PRSS21) to build the TRG prognostic model and nine hub genes (TMPO, SLC25A15, SCRG1, ISL1, SOD3, GAD1, LOXL4, AKR1C2, and MAGEA3) to build the ERG prognostic model. Additionally, the signature’s area under curve (AUC) values, survival rates, C-index scores, and mean squared error (RMS) curves were evaluated against those of previously published signatures, which revealed that the signature identified in this study performed comparably. Meanwhile, based on the IMvigor210 cohort, a statistically significant difference in OS between immunotherapy and risk scores was observed. It was followed by LASSO regression analysis which identified 17 key DEGs and a support vector machine (SVM) model identified 40 significant DEGs, and based on the Venn diagram, eight co-expression genes (ENPP6, VMP1, LY6E, SHISA6, TMEM158, SYT4, IL11, and KLK8) were discovered. Conclusion: The study identified some hub genes that could be useful in predicting prognosis and management in GC.

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“…In solid tumors, uPA and plasmin activities on the tumor cell surface promote tumor progression and metastasis [27], and aberrant expression of testisin could promote testisin-mediated uPA activation to enhance pro-metastatic tumor activities in vivo. Testisin overexpression is associated with ovarian cancer [14,15,65]. Fibrin is a significant component of ovarian tumor pathology [66], and ovarian cancerassociated ascites fluid is rich in cross-linked fibrin and fibrin degradation products.…”

Section: Discussionmentioning

confidence: 99%

Intersection of Coagulation and Fibrinolysis by the Glycosylphosphatidylinositol (GPI)-Anchored Serine Protease Testisin

Buzza,

Pawar,

Strong

et al. 2023

IJMS

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Hemostasis is a delicate balance between coagulation and fibrinolysis that regulates the formation and removal of fibrin, respectively. Positive and negative feedback loops and crosstalk between coagulation and fibrinolytic serine proteases maintain the hemostatic balance to prevent both excessive bleeding and thrombosis. Here, we identify a novel role for the glycosylphosphatidylinositol (GPI)-anchored serine protease testisin in the regulation of pericellular hemostasis. Using in vitro cell-based fibrin generation assays, we found that the expression of catalytically active testisin on the cell surface accelerates thrombin-dependent fibrin polymerization, and intriguingly, that it subsequently promotes accelerated fibrinolysis. We find that the testisin-dependent fibrin formation is inhibited by rivaroxaban, a specific inhibitor of the central prothrombin-activating serine protease factor Xa (FXa), demonstrating that cell-surface testisin acts upstream of factor X (FX) to promote fibrin formation at the cell surface. Unexpectedly, testisin was also found to accelerate fibrinolysis by stimulating the plasmin-dependent degradation of fibrin and enhancing plasmin-dependent cell invasion through polymerized fibrin. Testisin was not a direct activator of plasminogen, but it is able to induce zymogen cleavage and the activation of pro-urokinase plasminogen activator (pro-uPA), which converts plasminogen to plasmin. These data identify a new proteolytic component that can regulate pericellular hemostatic cascades at the cell surface, which has implications for angiogenesis, cancer biology, and male fertility.

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Testisin, a Glycosyl-Phosphatidylinositol–Linked Serine Protease, Promotes Malignant Transformation In vitro and In vivo

Cited by 33 publications

References 40 publications

Targeted Analysis of Protein Termini

Targeted Analysis of Protein Termini

Epigenetic and Tumor Microenvironment for Prognosis of Patients with Gastric Cancer

Intersection of Coagulation and Fibrinolysis by the Glycosylphosphatidylinositol (GPI)-Anchored Serine Protease Testisin

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