ArticleProceedings of the National Academy of Sciences of the United States of America2013
N terminus of ASPP2 binds to Ras and enhances Ras/Raf/MEK/ERK activation to promote oncogene-induced senescence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Mir-30b-5p Promotes Proliferation, Migration, and Invasion of Breast Cancer Cells via Targeting ASPP2.BioMed research international · 2020Trial
- TP53BP2: Roles in suppressing tumorigenesis and therapeutic opportunities.Genes & diseases · 2023Review
- Targeted splicing therapy: new strategies for colorectal cancer.Frontiers in oncology · 2023Review
- RDIVpSGP motif of ASPP2 binds to 14-3-3 and enhances ASPP2/k18/14-3-3 ternary complex formulation to promote BRAF/MEK/ERK signal inhibited cell proliferation in hepatocellular carcinoma.Cancer gene therapy · 2022Article
- Afadin couples RAS GTPases to the polarity rheostat Scribble.Nature communications · 2022Article
- Article
- Proximity proteomics identifies PAK4 as a component of Afadin-Nectin junctions.Nature communications · 2021Article
- ASPP2κ Is Expressed In Human Colorectal Carcinoma And Promotes Chemotherapy Resistance And Tumorigenesis.Frontiers in molecular biosciences · 2021Article
- The Small GTPase RAC1B: A Potent Negative Regulator of-and Useful Tool to Study-TGFβ Signaling.Cancers · 2020Review
- CagA-ASPP2 complex mediates loss of cell polarity and favorsProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Advances in Lung Cancer Driver Genes Associated With Brain Metastasis.Frontiers in oncology · 2020Review
- ASPP2 inhibits tumor growth by repressing the mevalonate pathway in hepatocellular carcinoma.Cell death & disease · 2019Article
- Inhibition of lung cancer cells and Ras/Raf/MEK/ERK signal transduction by ectonucleoside triphosphate phosphohydrolase-7 (ENTPD7).Respiratory research · 2019Article
- Proximity biotinylation identifies a set of conformation-specific interactions between Merlin and cell junction proteins.Science signaling · 2019Article
- Alternative splicing of the tumor suppressor ASPP2 results in a stress-inducible, oncogenic isoform prevalent in acute leukemia.EBioMedicine · 2019Article
- Mechanisms shaping the role of ERK1/2 in cellular senescence (Review).Molecular medicine reports · 2019Review
- Baicalin induces cellular senescence in human colon cancer cells via upregulation of DEPP and the activation of Ras/Raf/MEK/ERK signaling.Cell death & disease · 2018Article
- Myelodysplastic syndrome in an infant with constitutional pure duplication 1q41-qter.Human genome variation · 2018Article
- Steady-State Levels of Phosphorylated Mitogen-Activated Protein Kinase Kinase 1/2 Determined by Mortalin/HSPA9 and Protein Phosphatase 1 Alpha inMolecular and cellular biology · 2017Article
- Notch activation enhances mesenchymal stem cell sheet osteogenic potential by inhibition of cellular senescence.Cell death & disease · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The ASPP2 (also known as 53BP2L) tumor suppressor is a proapoptotic member of a family of p53 binding proteins that functions in part by enhancing p53-dependent apoptosis via its C-terminal p53-binding domain. Mounting evidence also suggests that ASPP2 harbors important nonapoptotic p53-independent functions. Structural studies identify a small G protein Ras-association domain in the ASPP2 N terminus. Because Ras-induced senescence is a barrier to tumor formation in normal cells, we investigated whether ASPP2 could bind Ras and stimulate the protein kinase Raf/MEK/ERK signaling cascade. We now show that ASPP2 binds to Ras-GTP at the plasma membrane and stimulates Ras-induced signaling and pERK1/2 levels via promoting Ras-GTP loading, B-Raf/C-Raf dimerization, and C-Raf phosphorylation. These functions require the ASPP2 N terminus because BBP (also known as 53BP2S), an alternatively spliced ASPP2 isoform lacking the N terminus, was defective in binding Ras-GTP and stimulating Raf/MEK/ERK signaling. Decreased ASPP2 levels attenuated H-RasV12-induced senescence in normal human fibroblasts and neonatal human epidermal keratinocytes. Together, our results reveal a mechanism for ASPP2 tumor suppressor function via direct interaction with Ras-GTP to stimulate Ras-induced senescence in nontransformed human cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.