Nuclear actin assembly in steroid hormone receptor signaling

• Applicant: Professor Dr. Robert Grosse
• Subject Area: Pharmacology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 570488121

Nuclear actin has emerged as a dynamic and essential structural component, playing critical roles in chromatin dynamics, DNA repair, mitosis, replication stress, and transcriptional regulation. Recent advancements in actin probes and advanced microscopy techniques have enabled direct visualization of nuclear actin assembly events in living cells that were previously unknown. We previously discovered that nuclear actin assembly is crucially involved in androgen receptor signaling. Here I propose that nuclear actin structures play a general role for various steroid hormone receptors resembling a novel layer of regulation. Our ongoing work shows that nuclear actin dynamics drives functions of steroid hormone receptors such as estrogen, progesterone or corticosteroid receptors, all of which are of central pharmacological importance. Furthermore, members of the actin nucleating formin protein family appear to evolve into clinically relevant coactivators of steroid hormone receptors, thereby uncovering a novel mechanism in steroid hormone signaling. I thus aim to elucidate the molecular mechanisms driving actin-dependent steroid hormone signaling. Understanding these mechanisms will shed light on the emerging role of actin assembly for nuclear organization and transcription. These results shall pave the way for new concepts of future pharmacological interventions.

• DFG Programme: Reinhart Koselleck Projects