Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor.
Open accessAbstract
Whereas several apoptosis-related proteins have been linked to the antiapoptotic effects of Akt serine-threonine kinase, the search continues to explain the Akt signaling role in promoting cell survival via antiapoptotic effects. Here, we demonstrate that Akt phosphorylates the androgen receptor (AR) at Ser-210 and Ser-790. A mutation at AR Ser-210 results in the reversal of Akt-mediated suppression of AR transactivation. Activation of the phosphatidylinositol-3-OH kinase/Akt pathway results in the suppression of AR target genes, such as p21, and the decrease of androgen/AR-mediated apoptosis, which may involve the inhibition of interaction between AR and AR coregulators. Together, these findings provide a molecular basis for cross-talk between two signaling pathways at the level of Akt and AR-AR coregulators that may help us to better understand the roles of Akt in the androgen/AR-mediated apoptosis.
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Akt has both agonistic and antagonistic influence on AR activity, either through direct phosphorylation of the receptor or through the action of downstream effectors, in both the presence and absence of androgen.
“Akt has been shown to have both agonistic and antagonistic influence on AR activity, either through direct phosphorylation of the receptor or through the action of downstream effectors, in both the presence and absence of androgen (49 -51).”
From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [49]
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- Authors
- Lin, H.-K., Yeh, S., Kang, H.-Y., & Chang, C.
- Affiliations
- University of Rochester Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-06-12
- Volume
- 98
- Issue
- 13
- Pages
- 7200-7205
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC34646
- OpenAlex
- W2126071672
- Cited by
- 401
- References
- 36
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 15 · 2023: 11 · 2022: 11 · 2021: 5 · 2020: 7 · 2019: 8 · 2018: 6 · 2017: 13 · 2016: 16 · 2015: 14 · 2014: 12 · 2013: 18 · 2012: 24
- FWCI
- 22.84
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- Akt, androgen receptor, apoptosis, receptor phosphorylation, PI3K/Akt signaling, p21, signaling crosstalk, cell survival
- MeSH terms
- Chromones, Enzyme Inhibitors, Humans, Male, Morpholines, Phosphorylation, Prostatic Neoplasms, Proto-Oncogene Proteins, Receptors, Androgen, Recombinant Proteins, Serine, Dihydrotestosterone, Transfection, Tumor Cells, Cultured, Signal Transduction, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Mutagenesis, Site-Directed, Apoptosis, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Amino Acid Substitution, Proto-Oncogene Proteins c-akt, Androgen Receptor Antagonists
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