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Peptidyl Arginine Deiminase 2 (PADI2)-Mediated Arginine Citrullination Modulates Transcription in Cancer
Miguel Beato1,2, Priyanka Sharma1
1Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, 08003 Barcelona, Spain.
Abstract:
Protein arginine deimination leading to the non-coded amino acid citrulline remains a key question in the field of post-translational modifications ever since its discovery by Rogers and Simmonds in 1958. Citrullination is catalyzed by a family of enzymes called peptidyl arginine deiminases (PADIs). Initially, increased citrullination was associated with autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, as well as other neurological disorders and multiple types of cancer. During the last decade, research efforts have focused on how citrullination contributes to disease pathogenesis by modulating epigenetic events, pluripotency, immunity and transcriptional regulation. However, our knowledge regarding the functional implications of citrullination remains quite limited, so we still do not completely understand its role in physiological and pathological conditions. Here, we review the recently discovered functions of PADI2-mediated citrullination of the C-terminal domain of RNA polymerase II in transcriptional regulation in breast cancer cells and the proposed mechanisms to reshape the transcription regulatory network that promotes cancer progression.
Insights
Protein arginine deimination, catalyzed by peptidyl arginine deiminases (PADIs), creates citrulline. PADI2-mediated citrullination of RNA polymerase II impacts breast cancer transcriptional regulation.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Protein arginine deimination, producing citrulline, is a key post-translational modification.
- Initially linked to autoimmune and neurological diseases, and cancer, its precise roles are still being uncovered.
- Recent research explores citrullination's impact on epigenetics, immunity, and transcriptional regulation.
Purpose of the Study:
- To review the functions of PADI2-mediated citrullination.
- To elucidate mechanisms of citrullination in transcriptional regulation within breast cancer cells.
- To understand how citrullination reshapes the transcription regulatory network in cancer progression.
Main Methods:
- Literature review of recent studies on PADI2 and citrullination.
- Analysis of proposed mechanisms in breast cancer models.
- Focus on the C-terminal domain of RNA polymerase II.
Main Results:
- PADI2-mediated citrullination of RNA polymerase II's C-terminal domain is a newly discovered function.
- This modification plays a role in transcriptional regulation in breast cancer cells.
- Proposed mechanisms suggest a reshaped transcription regulatory network promoting cancer.
Conclusions:
- PADI2-mediated citrullination is a significant factor in breast cancer transcriptional regulation.
- Understanding these mechanisms can provide insights into cancer pathogenesis.
- Further research is needed to fully grasp citrullination's physiological and pathological implications.
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