m-sharma.bsky.social
@m-sharma.bsky.social
Reposted
Myofibrillogenesis Regulator‐1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin‐Protein Ligase Itchy Homolog in the Metastasis of Non‐Small Cell Lung Cancer
Myofibrillogenesis Regulator‐1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin‐Protein Ligase Itchy Homolog in the Metastasis of Non‐Small Cell Lung Cancer
The novel cancer related multifunctional protein MR-1 (Myofrillogenes regulator-1) can stabilize the expression of Notch3-ICD (NICD3) in the cytoplasm through ITCH, which can upregulate many genes related to metastasis to promote the metastasis of NSCLC cells. Interference with the interaction between MR-1 and NICD3 can increase the degradation of NICD3 and impair the metastatic ability of NSCLC cells. Abstract Myofibrillogenesis regulator-1 (MR-1) is a multifunctional protein involved in the development of various human tumors. The study is the first to report the promoting effect of MR-1 on the development and metastasis of non-small cell lung cancer (NSCLC). MR-1 is upregulated in NSCLC and positively associated with poor prognosis. The overexpression of MR-1 promotes the metastasis of NSCLC cells by stabilizing the expression of Notch3-ICD (NICD3) in the cytoplasm through enrichment analysis, in vitro and in vivo experimental researches. And Notch3 signaling can upregulate many genes related to metastasis. The stabilizing effect of MR-1 on NICD3 is achieved through the mono-ubiquitin lysosomal pathway and the specific E3 ubiquitin ligase is Itchy homolog (ITCH). There is a certain interaction between MR-1 and NICD3. Elevated MR-1 can affect the level of ITCH phosphorylation, reduce its E3 enzyme activity, and thus lead to reduce the ubiquitination and degradation of NICD3. Interference with the interaction between MR-1 and NICD3 can increase the degradation of NICD3 and impair the metastatic ability of NSCLC cells, which is a previously overlooked treatment option in NSCLC. In summary, interference with the interaction between MR-1 and NICD3 in the progression of lung cancer may be a promising therapeutic target.
onlinelibrary.wiley.com
February 12, 2024 at 9:07 AM
Reposted
The E3 ubiquitin ligase RNF216 contains a linear ubiquitin chain-determining-like domain that functions to regulate dendritic arborization and dendritic spine type in hippocampal neurons https://www.biorxiv.org/content/10.1101/2023.10.19.563080v1
The E3 ubiquitin ligase RNF216 contains a linear ubiquitin chain-determining-like domain that functions to regulate dendritic arborization and dendritic spine type in hippocampal neurons https://www.biorxiv.org/content/10.1101/2023.10.19.563080v1
Of the hundreds of E3 ligases found in the human genome, the RING-between RING (RBR) E3 ligase in th
www.biorxiv.org
October 20, 2023 at 6:17 AM
Reposted
Scientists used CRISPR gene-editing tools to safely disable a DNA mutation linked to chemo-resistant melanoma. The "edit" made cancer cells easier to treat & minimized side effect risks. This tumor-specific approach targets tumor cells & leaves healthy cells alone medicalxpress.com/news/2024-10...
Scientists use CRISPR tools to safely disable gene mutation linked to treatment-resistant melanoma
In a potential advance for melanoma patients, researchers at ChristianaCare's Gene Editing Institute have used CRISPR gene editing tools to disable a gene mutation often seen in aggressive forms of th...
medicalxpress.com
October 16, 2024 at 5:16 PM
Reposted
For many traits there is a correlation between the number of duplications or loss-of-function (LoF) mutations someone carries, and their phenotype. Curiously, for most traits, these effects are aligned in the SAME direction. Why?
November 12, 2024 at 6:10 AM
Reposted
Structural variants are ripe for interrogation using genome engineering. Jonas Koeppel Juliane Weller Thomas Vanderstichele (Wellcome Sanger Institute) and I review technology progress, insights gained to date, and challenges and promise for the road ahead. www.nature.com/articles/s41588-024-01981-7
Engineering structural variants to interrogate genome function - Nature Genetics
Structural variations (SVs) impact gene expression, genome stability and disease susceptibility. This Review discusses recent advances in genome-engineering tools that enable precise SV generation and...
www.nature.com
November 16, 2024 at 3:29 PM