The secreted inhibitor of invasive cell growth CREG1 is negatively regulated by cathepsin proteases

Gomez-Auli, Alejandro; Hillebrand, Larissa E.; Christen, D.; Günther, Sira C.; Biniossek, Martin L.; Peters, Christoph; Schilling, Oliver; Reinheckel, Thomas

doi:10.1007/s00018-020-03528-5

Cited by 3 publications

(2 citation statements)

References 102 publications

(186 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CTSB also induces cell senescence mediated malignant transformation via CCNB2/SASP/CTSB & PGE2 axis 44 . It was also shown that CTSB can promote proliferation by upregulating the expression of p-ERK and c-Myc and reducing the level of Cellular Repressor of E1A Stimulated Genes 1 in GBM 45 . CTSB can increases the resistance of glioma cells to apoptosis and ferroptosis via lysosome-nuclear pathway of communication 15 , 46 .…”

Section: Discussionmentioning

confidence: 99%

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

Chen

Liu

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Previous researches have demonstrated the meaning of CTSB for the progress of several tumors, whereas few clues about its immunological characteristic in gliomas. Here we systematically explored its biologic features and clinical significance for gliomas. 699 glioma cases of TCGA and 325 glioma cases of CGGA were respectively included as training and validating cohorts. R software was used for data analysis and mapping. We found that CTSB was remarkably highly-expressed for HGG, IDH wild type, 1p19q non-codeletion type, MGMT promoter unmethylation type and mesenchymal gliomas. CTSB could specifically and sensitively indicate mesenchymal glioma. Upregulated CTSB was an independent hazard correlated with poor survival. CTSB-related biological processes in gliomas chiefly concentrated on immunoreaction and inflammation response. Then we proved that CTSB positively related to most inflammatory metagenes except IgG, including HCK, LCK, MHC II, STAT1 and IFN. More importantly, the levels of glioma-infiltrating immune cells were positively associated with the expression of CTSB, especially for TAMs, MDSCs and Tregs. In conclusion, CTSB is closely related to the malignant pathological subtypes, worse prognosis, immune cells infiltration and immunosuppression of gliomas, which make it a promising biomarker and potential target in the diagnosis, treatment and prognostic assessment of gliomas.

show abstract

Section: Discussionmentioning

confidence: 99%

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

Chen

Liu

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…This gene, Creg1 (cellular repressor of E1A-stimulated genes), is upregulated in treated animals. Creg is considered to be a tumor suppressor and its upregulation should not be associated with cancer (39). Additional studies are required whether the modest upregulation of these genes is due to O 6 BG/BCNU treatment.…”

Section: Effect On Transcriptomementioning

confidence: 99%

In vivo base editing by a single i.v. vector injection for treatment of hemoglobinopathies

Li¹,

Georgakopoulou²,

Newby³

et al. 2022

JCI Insight

View full text Add to dashboard Cite

Individuals with -thalassemia or Sickle Cell Disease and hereditary persistence of fetal hemoglobin (HPFH) possessing 30% HbF appear to be symptom-free. Here, we used a non-integrating HDAd5/35++ vector expressing a highly efficient and accurate version of an adenine base editor (ABE8e) to install, in vivo, a -113A>G HPFH mutation in the -globin promoters in "healthy" CD46/-YAC mice carrying the human -globin locus. Our in vivo hematopoietic stem cell (HSC) editing/selection strategy involves only subcutaneous and intravenous injections and does not require myeloablation and HSC transplantation. In vivo HSC base editing in CD46/-YAC mice resulted in >60% -113A>G conversion with 30% -globin of globin expressed in 70% of erythrocytes. Importantly, no off-target editing at sites predicted by CIRCLE-Seq or in silico was detected. Furthermore, no critical alterations in the transcriptome of in vivo edited mice were found by RNA-seq. In vitro, in HSCs from -thalassemia and Sickle Cell Disease patients, transduction with the base editor vector mediated efficient -113 A>G conversion and reactivation of −globin expression with subsequent phenotypic correction of erythroid cells. Because our in vivo base editing strategy is safe and technically simple, it has the potential for clinical application in developing countries where hemoglobinopathies are prevalent. Key points-In vivo HSC transduction of -YAC mice with an ABE8e expressing HDAd5/35++ vector is safe and results in efficient and stable -globin reactivation in ~70% of erythrocytes at levels of 30% of human -globin.-Therapeutic editing is achieved in thalassemia and Sickle Cell Disease patient CD34 + cells with HDAd-EF1.ABE8e, leading to phenotypic correction in in vitro differentiated erythroid cells.

show abstract

Inheritance of H3K9 methylation regulates genome architecture in Drosophila early embryos

Atinbayeva,

Valent,

Zenk

et al. 2024

EMBO J

View full text Add to dashboard Cite

Constitutive heterochromatin is essential for transcriptional silencing and genome integrity. The establishment of constitutive heterochromatin in early embryos and its role in early fruitfly development are unknown. Lysine 9 trimethylation of histone H3 (H3K9me3) and recruitment of its epigenetic reader, heterochromatin protein 1a (HP1a), are hallmarks of constitutive heterochromatin. Here, we show that H3K9me3 is transmitted from the maternal germline to the next generation. Maternally inherited H3K9me3, and the histone methyltransferases (HMT) depositing it, are required for the organization of constitutive heterochromatin: early embryos lacking H3K9 methylation display de-condensation of pericentromeric regions, centromere-centromere de-clustering, mitotic defects, and nuclear shape irregularities, resulting in embryo lethality. Unexpectedly, quantitative CUT&Tag and 4D microscopy measurements of HP1a coupled with biophysical modeling revealed that H3K9me2/3 is largely dispensable for HP1a recruitment. Instead, the main function of H3K9me2/3 at this developmental stage is to drive HP1a clustering and subsequent heterochromatin compaction. Our results show that HP1a binding to constitutive heterochromatin in the absence of H3K9me2/3 is not sufficient to promote proper embryo development and heterochromatin formation. The loss of H3K9 HMTs and H3K9 methylation alters genome organization and hinders embryonic development.

show abstract

The secreted inhibitor of invasive cell growth CREG1 is negatively regulated by cathepsin proteases

Cited by 3 publications

References 102 publications

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

In vivo base editing by a single i.v. vector injection for treatment of hemoglobinopathies

Inheritance of H3K9 methylation regulates genome architecture in Drosophila early embryos

Contact Info

Product

Resources

About