| Autor: |
Baylee A. Porter, Xiang Li, Neeru Arya, Fan Zhang, Sonia H.Y. Kung, Ladan Fazli, Htoo Zarni Oo, Yinan Li, Kenneth Marincin, Konsta Kukkonen, Henna Urhonen, Maria A. Ortiz, Allysa P. Kemraj, Eva Corey, Xuesen Dong, Vladimir A. Kuznetsov, Matti Nykter, Martin E. Gleave, Gennady Bratslavsky, Alfonso Urbanucci, Dominique Frueh, Alaji Bah, Leszek Kotula |
| Rok vydání: |
2023 |
| DOI: |
10.1101/2023.05.26.542350 |
| Popis: |
Transcription regulates key functions of living organisms in normal and disease states, including cell growth and development, embryonic and adult tissue organization, and tumor progression. Here we identify a novel mechanism of transcriptional regulation by an actin regulatory and signaling protein, Abelson Interactor 1 (ABI1). Using prostate cancer models, we uncover a reciprocal regulation between ABI1 and the Androgen Receptor (AR). ABI1 is a direct, androgen-regulated target; in turn, ABI1 interacts with AR and its splice variant ARv7, and co-regulates a subset of specific transcriptional targets. ABI1 directs transcription through transient yet well-defined interaction of its intrinsically disordered region with DNA. Clinical evaluation shows that the ABI1-DNA binding (through Exon 4 splicing) and ABI1-AR interaction are regulated during androgen deprivation therapy and prostate cancer progression, thus controlling tumor plasticity through connecting actin cytoskeleton and cellular signaling to transcriptional regulation. We propose ABI1 as epigenetic regulator of transcriptional homeostasis in AR-driven cancers. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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