Taspase 1: A protease with many biological surprises

Niizuma, Hidetaka; Cheng, Emily H.; Hsieh, James J.

doi:10.1080/23723556.2014.999513

Cited by 20 publications

(34 citation statements)

References 10 publications

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“…TASP1 is classified as a "non-oncogene addiction" protease and plays an important role in various cancer development [20,23]. Herein, we for the first time found that TASP1 is highly expressed in GBC tissues compared with the matched non-malignant tissues.…”

Section: Discussionmentioning

confidence: 83%

“…Taspase 1 (threonine aspartase 1; TASP1) was initially identified as an endopeptidase responsible for cleaving mixed lineage leukemia 1 (MLL1) protein for proper regulation of HOX expression [20,21]. Other genetically and biochemically proven TASP1 substrates include MLL2, TFIIAα-β, ALFα-β, and Drosophila HCF-1 [22][23][24]. Interestingly, all of these substrates are broad-acting nuclear factors that regulate gene expression, suggesting a critical role for TASP1 in the orchestration of various biological processes [23].…”

Section: Ivyspring International Publishermentioning

confidence: 99%

“…Other genetically and biochemically proven TASP1 substrates include MLL2, TFIIAα-β, ALFα-β, and Drosophila HCF-1 [22][23][24]. Interestingly, all of these substrates are broad-acting nuclear factors that regulate gene expression, suggesting a critical role for TASP1 in the orchestration of various biological processes [23]. TASP1 drives cell cycle progression and coordinates cell proliferation and apoptosis [19].…”

Section: Ivyspring International Publishermentioning

confidence: 99%

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TASP1 Promotes Gallbladder Cancer Cell Proliferation and Metastasis by Up-regulating FAM49B via PI3K/AKT Pathway

Zhang

Yang

et al. 2020

Int. J. Biol. Sci.

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The highly conserved protease TASP1 not only takes part in critical site-specific proteolysis, but also plays an important role in numerous liquid and solid malignancies. However, the TASP1 expression and its biological regulation function in malignant gallbladder carcinoma (GBC) remain fully unknown. Here we observed that TASP1 levels were substantially overexpressed in GBC samples compared with non-tumor tissues. High TASP1 level was closely associated with T stage and metastasis, and was also correlated with poor prognosis in GBC patients. The depletion of TASP1 inhibited GBC cell proliferation and metastasis in vitro and in vivo. Furthermore, we first revealed that FAM49B had biological function and was positively regulated by TASP1 activating PI3K/AKT signaling pathway in GBC. At the same time, FAM49B also promoted GBC cell proliferation and migration. Inhibition of PI3K/AKT with LY294002 or FAM49B expression abrogated Myc-TASP1/Lv-shTASP1-induced GBC cell proliferation and motility. In conclusion, these findings demonstrate that TASP1 is critical for GBC progression via TASP1-PI3K/AKT-FAM49B axis and it may be a novel prognostic factor. The therapeutic targeting TASP1 may be a potential treatment approach for GBC patients.

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Section: Discussionmentioning

confidence: 83%

Section: Ivyspring International Publishermentioning

confidence: 99%

Section: Ivyspring International Publishermentioning

confidence: 99%

See 1 more Smart Citation

TASP1 Promotes Gallbladder Cancer Cell Proliferation and Metastasis by Up-regulating FAM49B via PI3K/AKT Pathway

Zhang

Yang

et al. 2020

Int. J. Biol. Sci.

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“…The proteolytic cleavage activation of GTFIIA is essential for male spermatogenesis, craniofacial development, and maintenance of fetal liver hematopoietic stem cells. 10 The role of taspase 1 is further supported by studying taspase 1 −/− mice model which showed early postnatal lethality, skeletal abnormalities, and in utero and postnatal growth failure. 11 Although this phenotype seems to be more severe than that of the infant described here, the vital role (Table 1).…”

Section: Methodsmentioning

confidence: 99%

TASP1 is deleted in an infant with developmental delay, microcephaly, distinctive facial features, and multiple congenital anomalies

Suleiman

Mundt²,

Sampath³

et al. 2018

Clinical Genetics

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We report a 20p12.1 homozygous deletion including exons 5-10 of the TASP1 gene in an infant with developmental delay, acquired microcephaly, distinctive facial features, and multiple congenital anomalies involving skeletal, cardiac, and renal systems. TASP1 encodes taspase 1 which is responsible for cleaving, thus activating, a number of transcription factors including the mixed lineage leukemia 1 (MLL1). Taspase 1-deficient mice showed early lethality, skeletal abnormalities, and growth failure, which support a potentially causal role of TASP1 deletion in this infant. Furthermore, the infant reported here had many of the features seen in Wiedemann-Steiner syndrome which is caused by MLL1 defects. Such observation further supports that TASP1 is a novel disease-related gene that is associated with a disease phenotype overlapping with Wiedemann-Steiner syndrome as both are caused by defects in the same pathway.

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“…Taspase is a conserved threonine-aspartic acid protease that cleaves mammalian and Drosophila MLL1/trithorax, as well as other nuclear proteins ( e.g. , TFIIA) associated with chromatin and transcription; mutations in human Taspase1 have been associated with certain forms of cancer, particularly those of the head and neck ( Hsieh et al 2003a ; Hsieh et al 2003b ; Khan et al 2005 ; Takeda et al 2006 ; Zhou et al 2006 ; Oyama et al 2013 ; Niizuma et al 2015 ; Takeda et al 2015 ; Stauber et al 2016 ; Gribko et al 2017 ). The four independent mutations are placed on the tasp-1 genomic locus as shown in Figure 5A .…”

Section: Resultsmentioning

confidence: 99%

A Strategy To Isolate Modifiers ofCaenorhabditis elegansLethal Mutations: Investigating the Endoderm Specifying Ability of the Intestinal Differentiation GATA Factor ELT-2

Wiesenfahrt

Duanmu

Snider

et al. 2018

G3 Genes|Genomes|Genetics

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The ELT-2 GATA factor normally functions in differentiation of the C. elegans endoderm, downstream of endoderm specification. We have previously shown that, if ELT-2 is expressed sufficiently early, it is also able to specify the endoderm and to replace all other members of the core GATA-factor transcriptional cascade (END-1, END-3, ELT-7). However, such rescue requires multiple copies (and presumably overexpression) of the end-1p::elt-2 cDNA transgene; a single copy of the transgene does not rescue. We have made this observation the basis of a genetic screen to search for genetic modifiers that allow a single copy of the end-1p::elt-2 cDNA transgene to rescue the lethality of the end-1end-3 double mutant. We performed this screen on a strain that has a single copy insertion of the transgene in an end-1end-3 background. These animals are kept alive by virtue of an extrachromosomal array containing multiple copies of the rescuing transgene; the extrachromosomal array also contains a toxin under heat shock control to counterselect for mutagenized survivors that have been able to lose the rescuing array. A screen of ∼14,000 mutagenized haploid genomes produced 17 independent surviving strains. Whole genome sequencing was performed to identify genes that incurred independent mutations in more than one surviving strain. The C. elegans gene tasp-1 was mutated in four independent strains. tasp-1 encodes the C. elegans homolog of Taspase, a threonine-aspartic acid protease that has been found, in both mammals and insects, to cleave several proteins involved in transcription, in particular MLL1/trithorax and TFIIA. A second gene, pqn-82, was mutated in two independent strains and encodes a glutamine-asparagine rich protein. tasp-1 and pqn-82 were verified as loss-of-function modifiers of the end-1p::elt-2 transgene by RNAi and by CRISPR/Cas9-induced mutations. In both cases, gene loss leads to modest increases in the level of ELT-2 protein in the early endoderm although ELT-2 levels do not strictly correlate with rescue. We suggest that tasp-1 and pqn-82 represent a class of genes acting in the early embryo to modulate levels of critical transcription factors or to modulate the responsiveness of critical target genes. The screen’s design, rescuing lethality with an extrachromosomal transgene followed by counterselection, has a background survival rate of <10−4 without mutagenesis and should be readily adapted to the general problem of identifying suppressors of C. elegans lethal mutations.

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Taspase 1: A protease with many biological surprises

Cited by 20 publications

References 10 publications

TASP1 Promotes Gallbladder Cancer Cell Proliferation and Metastasis by Up-regulating FAM49B via PI3K/AKT Pathway

TASP1 Promotes Gallbladder Cancer Cell Proliferation and Metastasis by Up-regulating FAM49B via PI3K/AKT Pathway

TASP1 is deleted in an infant with developmental delay, microcephaly, distinctive facial features, and multiple congenital anomalies

A Strategy To Isolate Modifiers ofCaenorhabditis elegansLethal Mutations: Investigating the Endoderm Specifying Ability of the Intestinal Differentiation GATA Factor ELT-2

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