Taspase1: a 'misunderstood' protease with translational cancer relevance
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- D Wuensch
- A Hahlbrock
- S Jung
- T Schirmeister
- J van den Boom
- O Schilling
- SK Knauer
- RH Stauber
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000379270100001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1038/onc.2015.436
- eISSN
- 1476-5594
- Externe Identifier
- Clarivate Analytics Document Solution ID: DQ5UI
- PubMed Identifier: 26657154
- ISSN
- 0950-9232
- Ausgabe der Veröffentlichung
- 26
- Zeitschrift
- ONCOGENE
- Paginierung
- 3351 - 3364
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Titel
- Taspase1: a 'misunderstood' protease with translational cancer relevance
- Sub types
- Review
- Ausgabe der Zeitschrift
- 35
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- D Wünsch
- A Hahlbrock
- S Jung
- T Schirmeister
- J van den Boom
- O Schilling
- SK Knauer
- RH Stauber
- DOI
- 10.1038/onc.2015.436
- eISSN
- 1476-5594
- ISSN
- 0950-9232
- Ausgabe der Veröffentlichung
- 26
- Zeitschrift
- Oncogene
- Sprache
- en
- Online publication date
- 2015
- Paginierung
- 3351 - 3364
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1038/onc.2015.436
- Datum der Datenerfassung
- 2022
- Titel
- Taspase1: a 'misunderstood' protease with translational cancer relevance
- Ausgabe der Zeitschrift
- 35
Datenquelle: Crossref
- Abstract
- Proteolysis is not only a critical requirement for life, but the executing enzymes also play important roles in numerous pathological conditions, including cancer. Therefore, targeting proteases is clearly relevant for improving cancer patient care. However, to effectively control proteases, a profound knowledge of their mechanistic function as well as their regulation and downstream signalling in health and disease is required. The highly conserved protease Threonine Aspartase1 (Taspase1) is overexpressed in numerous liquid and solid malignancies and was characterized as a 'non-oncogene addiction' protease. Although Taspase1 was shown to cleave various regulatory proteins in humans as well as leukaemia provoking mixed lineage leukaemia fusions, our knowledge on its detailed functions and the underlying mechanisms contributing to cancer is still incomplete. Despite superficial similarity to type 2 asparaginases as well as Ntn proteases, such as the proteasome, Taspase1-related research so far gives us the picture of a unique protease exhibiting special features. Moreover, neither effective genetic nor chemical inhibitors for this enzyme are available so far, thus hampering not only to further dissect Taspase1's pathobiological functions but also precluding the assessment of its clinical impact. Based on recent insights, we here critically review the current knowledge of Taspase1's structure-function relationship and its mechanistic relevance for tumorigenesis obtained from in vitro and in vivo cancer models. We provide a comprehensive overview of tumour entities for which Taspase1 might be of predictive and therapeutic value, and present the respective experimental evidence. To stimulate progress in the field, a comprehensive overview of Taspase1 targeting approaches is presented, including coverage of Taspase1-related patents. We conclude by discussing future inhibition strategies and relevant challenges, which need to be resolved by the field.
- Addresses
- Molecular and Cellular Oncology, ENT/University Medical Center of Mainz, Mainz, Germany.
- Autoren
- D Wünsch
- A Hahlbrock
- S Jung
- T Schirmeister
- J van den Boom
- O Schilling
- SK Knauer
- RH Stauber
- DOI
- 10.1038/onc.2015.436
- eISSN
- 1476-5594
- Externe Identifier
- PubMed Identifier: 26657154
- Open access
- false
- ISSN
- 0950-9232
- Ausgabe der Veröffentlichung
- 26
- Zeitschrift
- Oncogene
- Schlüsselwörter
- Humans
- Neoplasms
- Endopeptidases
- Aspartate Ammonia-Lyase
- Threonine
- Enzyme Inhibitors
- Gene Expression Regulation, Enzymologic
- Gene Expression Regulation, Neoplastic
- Molecular Structure
- Translational Research, Biomedical
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2015
- Paginierung
- 3351 - 3364
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Datum der Datenerfassung
- 2015
- Titel
- Taspase1: a 'misunderstood' protease with translational cancer relevance.
- Sub types
- Review
- Journal Article
- Ausgabe der Zeitschrift
- 35
Datenquelle: Europe PubMed Central
- Abstract
- Proteolysis is not only a critical requirement for life, but the executing enzymes also play important roles in numerous pathological conditions, including cancer. Therefore, targeting proteases is clearly relevant for improving cancer patient care. However, to effectively control proteases, a profound knowledge of their mechanistic function as well as their regulation and downstream signalling in health and disease is required. The highly conserved protease Threonine Aspartase1 (Taspase1) is overexpressed in numerous liquid and solid malignancies and was characterized as a 'non-oncogene addiction' protease. Although Taspase1 was shown to cleave various regulatory proteins in humans as well as leukaemia provoking mixed lineage leukaemia fusions, our knowledge on its detailed functions and the underlying mechanisms contributing to cancer is still incomplete. Despite superficial similarity to type 2 asparaginases as well as Ntn proteases, such as the proteasome, Taspase1-related research so far gives us the picture of a unique protease exhibiting special features. Moreover, neither effective genetic nor chemical inhibitors for this enzyme are available so far, thus hampering not only to further dissect Taspase1's pathobiological functions but also precluding the assessment of its clinical impact. Based on recent insights, we here critically review the current knowledge of Taspase1's structure-function relationship and its mechanistic relevance for tumorigenesis obtained from in vitro and in vivo cancer models. We provide a comprehensive overview of tumour entities for which Taspase1 might be of predictive and therapeutic value, and present the respective experimental evidence. To stimulate progress in the field, a comprehensive overview of Taspase1 targeting approaches is presented, including coverage of Taspase1-related patents. We conclude by discussing future inhibition strategies and relevant challenges, which need to be resolved by the field.
- Date of acceptance
- 2015
- Autoren
- D Wünsch
- A Hahlbrock
- S Jung
- T Schirmeister
- J van den Boom
- O Schilling
- SK Knauer
- RH Stauber
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/26657154
- DOI
- 10.1038/onc.2015.436
- eISSN
- 1476-5594
- Ausgabe der Veröffentlichung
- 26
- Zeitschrift
- Oncogene
- Schlüsselwörter
- Aspartate Ammonia-Lyase
- Endopeptidases
- Enzyme Inhibitors
- Gene Expression Regulation, Enzymologic
- Gene Expression Regulation, Neoplastic
- Humans
- Molecular Structure
- Neoplasms
- Threonine
- Translational Research, Biomedical
- Sprache
- eng
- Country
- England
- Paginierung
- 3351 - 3364
- PII
- onc2015436
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2017
- Titel
- Taspase1: a 'misunderstood' protease with translational cancer relevance.
- Sub types
- Journal Article
- Review
- Ausgabe der Zeitschrift
- 35
Datenquelle: PubMed
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