ArticleMolecular and cellular biology1998
Involvement of microtubules in the regulation of Bcl2 phosphorylation and apoptosis through cyclic AMP-dependent protein kinase.
Article in Molecular and cellular biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 365 citations in OpenAlex.
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- Involvement of AMPKα and MAPK-ERK/-JNK Signals in Docetaxel-Induced Human Tongue Squamous Cell Carcinoma Cell Apoptosis.International journal of molecular sciences · 2022Article
- Susceptibility of cytoskeletal-associated proteins for tumor progression.Cellular and molecular life sciences : CMLS · 2021Review
- Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics.Nature communications · 2021Article
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- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Chromosomal instability reducing effect of paclitaxel and lapatinib in mouse embryonic stem cells with chromosomal abnormality.Molecular biology reports · 2020Article
- α-Mangostin-encapsulated PLGA nanoparticles inhibit colorectal cancer growth by inhibiting Notch pathway.Journal of cellular and molecular medicine · 2020Article
- Topological properties and in vitro identification of essential nodes of the Paclitaxel and Vincristine interactomes in PC-3 cells.Biomedical journal · 2019Article
- Simulated microgravity induces nuclear translocation of Bax and BCL-2 in glial cultured C6 cells.Heliyon · 2019Article
- Protective action of N-acetylcysteine on sperm quality in cyclophosphamide-induced testicular toxicity in male Wistar rats.JBRA assisted reproduction · 2019Article
- Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes.Cell death & disease · 2018Article
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- Suppression of phosphorylated MAPK and caspase 3 by carbon dioxide.Molecular and cellular biochemistry · 2017Article
- Microtubule destabilising agents: far more than just antimitotic anticancer drugs.British journal of clinical pharmacology · 2017Review
- A Role for cAMP and Protein Kinase A in Experimental Necrotizing Enterocolitis.The American journal of pathology · 2017Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Bcl2 family of proteins plays a significant role in regulation of apoptosis. In this study, the microtubule-damaging drugs paclitaxel, vincristine, and vinblastine induced Bcl2 hyperphosphorylation and apoptosis in MCF-7 and MDA-MB-231 cells and reduced Bcl2-Bax dimerization. Paclitaxel or vincristine induced increased expression of Bax, while overexpression of Bcl2 in these cell lines counteracted the effects of low doses of these drugs. In addition, paclitaxel- and vincristine-induced activation of cyclic AMP (cAMP)-dependent protein kinase (protein kinase A [PKA]) induced Bcl2 hyperphosphorylation and apoptosis, which were blocked by the PKA inhibitor Rp diastereomers of cAMP (Rp-cAMP). This finding suggests that activation of PKA due to microtubule damage is an important event in Bcl2 hyperphosphorylation and induction of apoptosis. These microtubule-damaging drugs caused growth arrest in G2-M phase of the cell cycle and had no effect on p53 induction, suggesting that hyperphosphorylation mediated inactivation of Bcl2 and apoptosis without the involvement of p53. By comparison, the DNA-damaging drugs methotrexate and doxorubicin had no effect on Bcl2 hyperphosphorylation but induced p53 expression. Interestingly, paclitaxel or vincristine induced activation of caspase 3 and cleavage of poly(ADP-ribose) polymerase downstream of Bcl2 hyperphosphorylation. These data suggest that there may be a signaling cascade induced by agents that disrupt or damage the cytoskeleton that is distinct from (i.e., p53 independent), but perhaps related to (i.e., involves kinase activation and leads to apoptosis), the cellular response to DNA damage.
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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.