Dihydroartemisinin, active metabolite of artemether and artesunate

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

The Estrogen Receptor (ER) and Androgen Receptor (AR) are nuclear hormone receptors that function as transcription factors while Tyrosyl-DNA phosphodiesterase 1 (TDP1) is involved in DNA repair processes. ER also known as ESR1 and AR have a similar mechanistic role as they bind estradiol and dihydrotestosterone respectively influencing gene expression profiles. TDP1 weighing around 60 kDa repairs topoisomerase I-DNA covalent complexes by processing DNA breaks. ER and AR are highly expressed in hormone-responsive tissues like the breast prostate and ovary whereas TDP1 is ubiquitously present in the nucleus.

Biological function summary

Both Estrogen and Androgen Receptors modulate growth differentiation and reproductive functions. They function as homodimers or heterodimers within larger transcriptional complexes to regulate gene networks. TDP1 part of the DNA repair machinery maintains genome stability through interaction with proteins such as PARP1 and XRCC1. These activities underline their importance in cellular processes and homeostasis mediated through changing gene expression and repairing damaged DNA.

Pathways

The Estrogen and Androgen Receptors play significant roles in the estrogen signaling and androgen signaling pathways. These pathways affect cell proliferation and apoptosis via interactions with proteins like c-Myc and Cyclin D1. TDP1 is integral to the single-strand break repair pathway facilitating the resolution of topoisomerase I-DNA adducts by partnering with proteins like PNKP and Ligase III. These interactions highlight how these receptors and enzymes coordinate complex biological processes.

Estrogen and Androgen Receptors are connected to breast cancer and prostate cancer respectively as their dysregulation leads to unchecked cell division. ER is commonly overexpressed in breast cancer often alongside the cofactor coactivator protein SRC-3 which facilitates tumor progression. AR in prostate cancer interacts with proteins like FKBP5 that modulate hormone signaling pathways. TDP1 while not directly linked to cancer shows relevance in neurodegenerative disorders like Spinocerebellar Ataxia where its relationship with proteins like mutant ataxin-3 influences disease progression through defective DNA repair mechanisms.