The impact of <scp><i>SETBP1</i></scp> mutations in neurological diseases and cancer

Kohyanagi, Naoki; Ohama, Takashi

doi:10.1111/gtc.13057

Cited by 4 publications

(5 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SETBP1 (SET binding protein 1) stabilizes SET protein by blocking its cleavage by proteases. SET is a multifunctional protein that acts as a cancer-promoting factor and inhibitor of protein phosphatase 2A (PP2A), a major serine/threonine protein phosphatase [73]. PP2A is involved in hepatic gluconeogenesis, probably via PP2A-AMPK-FoxO1 signal-ing [74,75].…”

Section: Genes/proteins Identified By 1-l Transcription Of N-(aa)n-c ...mentioning

confidence: 99%

See 1 more Smart Citation

1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit

Nahalka

2024

IJMS

View full text Add to dashboard Cite

The COVID-19 pandemic prompted rapid research on SARS-CoV-2 pathogenicity. Consequently, new data can be used to advance the molecular understanding of SARS-CoV-2 infection. The present bioinformatics study discusses the “spikeopathy” at the molecular level and focuses on the possible post-transcriptional regulation of the SARS-CoV-2 spike protein S1 subunit in the host cell/tissue. A theoretical protein–RNA recognition code was used to check the compatibility of the SARS-CoV-2 spike protein S1 subunit with mRNAs in the human transcriptome (1-L transcription). The principle for this method is elucidated on the defined RNA binding protein GEMIN5 (gem nuclear organelle-associated protein 5) and RNU2-1 (U2 spliceosomal RNA). Using the method described here, it was shown that 45% of the genes/proteins identified by 1-L transcription of the SARS-CoV-2 spike protein S1 subunit are directly linked to COVID-19, 39% are indirectly linked to COVID-19, and 16% cannot currently be associated with COVID-19. The identified genes/proteins are associated with stroke, diabetes, and cardiac injury.

show abstract

Section: Genes/proteins Identified By 1-l Transcription Of N-(aa)n-c ...mentioning

confidence: 99%

“…The S1 subunit represses SETBP1 (Figure 3). SETBP1 functions as a stabilizer of the SET protein [73], which is an inhibitor of PP2A. The repression of SETBP1 activates PP2A-FOXO1 signaling, and the key gluconeogenic TF FOXO1 subsequently activates hepatic gluconeogenesis [74].…”

Section: T2d and Cardiac Stressmentioning

confidence: 99%

1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit

Nahalka

2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Furthermore, the AT hooks of SETBP1 allow DNA binding and gene expression activation through the formation of an epigenetic complex composed of SETBP1, PHF8, KMT2A, and HCF1 [2]. Different pathogenic variants in SETBP1 can result in three distinct diseases [4]. Germline variants cause two unique ultra-rare, de novo pediatric diseases: Schinzel Giedion Syndrome (SGS) [5] and SETBP1 haploinsufficiency disorder (SETBP1-HD) [6].…”

Section: Introductionmentioning

confidence: 99%

The landscape of SETBP1 gene expression and transcription factor activity across human tissues

Whitlock,

Wilk,

Howton

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

The SET binding protein 1 (SETBP1) gene encodes a transcription factor (TF) involved in various cellular processes. Variants in SETBP1 can result in three different diseases determined by the introduction (germline vs. somatic) and location of the variant. Germline variants cause the ultra-rare pediatric Schinzel Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disorder (SETBP1-HD), characterized by severe multisystemic abnormalities with neurodegeneration or a less severe brain phenotype accompanied by hypotonia and strabismus, respectively. Somatic variants in SETBP1 are associated with hematological malignancies and cancer development in other tissues in adults. To better understand the tissue-specific mechanisms involving SETBP1, we analyzed publicly available RNA-sequencing (RNA-seq) data from the Genotype-Tissue Expression (GTEx) project. We found SETBP1 and its known target genes were widely expressed across 31 adult human tissues. K-means clustering identified three distinct expression patterns of SETBP1 targets across tissues. Functional enrichment analysis (FEA) of each cluster revealed gene sets related to transcriptional regulation, DNA binding, and mitochondrial function. TF activity analysis of SETBP1 and its target TFs revealed tissue-specific TF activity, underscoring the role of tissue context-driven regulation and suggesting its impact in SETBP1-associated disease. In addition to uncovering tissue-specific molecular signatures of SETBP1 expression and TF activity, we provide a Shiny web application to facilitate exploring TF activity across human tissues for 758 TFs. This study provides insight into the landscape of SETBP1 expression and TF activity across 31 non-diseased human tissues and reveals tissue-specific expression and activity of SETBP1 and its targets. In conjunction with the web application we constructed, our framework enables researchers to generate hypotheses related to the role tissue backgrounds play with respect to gene expression and TF activity in different disease contexts.

show abstract

“…As a protein, it has a role in DNA replication and transcriptional regulation (Piazza et al, 2018). Different pathogenic variants in SETBP1 can result in three distinct diseases (Kohyanagi & Ohama, 2023). Germline variants cause two unique ultra-rare, de novo pediatric diseases: Schinzel Giedion Syndrome (SGS) (Schinzel & Giedion, 1978) and SETBP1 haploinsufficiency disorder ( SETBP1 -HD) (Morgan et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…(Piazza et al, 2018) Different pathogenic variants in SETBP1 can result in three distinct diseases. (Kohyanagi & Ohama, 2023) Germline variants cause two unique ultra-rare, de novo pediatric diseases: Schinzel Giedion Syndrome (SGS) (Schinzel & Giedion, 1978) and Setbp1 haploinsufficiency disorder (SETBP1-HD). (Morgan et al, 2021) These conditions are differentiated by location, phenotypic severity, and accompanying gain or loss of function (GoF, LoF), respectively.…”

Section: Introductionmentioning

confidence: 99%

The landscape ofSETBP1gene expression and transcription factor activity across human tissues

Whitlock¹,

Wilk²,

Howton³

et al. 2023

Preprint

View full text Add to dashboard Cite

The SET binding protein 1 (SETBP1) gene encodes a transcription factor (TF) involved in various cellular processes. Distinct SETBP1 variants have been linked to three different diseases. Germline variants cause the ultra-rare pediatric Schinzel Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disorder (SETBP1-HD), characterized by severe multisystemic abnormalities with neurodegeneration or a less severe brain phenotype accompanied by hypotonia and strabismus, respectively. Somatic variants in SETBP1 are associated with hematological malignancies and cancer development in other tissues in adults. To better understand the tissue-specific mechanisms involving SETBP1, we analyzed publicly available RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project. We found SETBP1 and its known target genes were widely expressed across 31 adult human tissues. Hierarchical clustering identified 3 distinct expression patterns of SETBP1 targets across tissues. Functional enrichment analysis revealed gene sets related to transcription regulation, DNA binding, and mitochondrial function. TF activity analysis of SETBP1 and its target TFs revealed tissue-specific TF activity, underscoring the role of tissue context-driven regulation and suggesting its impact in SETBP1-associated disease. In addition to uncovering tissue-specific molecular signatures of SETBP1 expression and TF activity, we provide a Shiny web application to facilitate the exploration of TF activity across human tissues for 758 TFs.

show abstract

The impact of SETBP1 mutations in neurological diseases and cancer

Cited by 4 publications

References 111 publications

1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit

1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit

The landscape of SETBP1 gene expression and transcription factor activity across human tissues

The landscape ofSETBP1gene expression and transcription factor activity across human tissues

Contact Info

Product

Resources

About