Cell cycle and apoptosis regulator 2 at the interface between DNA damage response and cell physiology

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Cell cycle and apoptosis regulator 2 (CCAR2), also known as DBC1, is a key protein in the DNA damage response (DDR).
• Upon genotoxic stress, CCAR2 interacts with SIRT1, influencing p53 acetylation and apoptosis.
• CCAR2 plays roles beyond DDR, including transcriptional regulation and circadian rhythm modulation.

Purpose of the Study:

• To review the multifaceted functions of CCAR2 in DNA damage response.
• To explore CCAR2's diverse biological activities in unstressed cells.
• To discuss the complex and often contradictory role of CCAR2 in cancer.

Main Methods:

• Literature review of studies on CCAR2 function.
• Analysis of CCAR2 interactions with key cellular proteins (ATM, ATR, SIRT1, p53, transcription factors, epigenetic modifiers).
• Examination of CCAR2's role in various cellular pathways including DNA repair, transcription, circadian rhythm, metabolism, and immunity.

Main Results:

• CCAR2 phosphorylation by ATM/ATR upon DNA damage inhibits SIRT1, activating p53 and promoting apoptosis.
• CCAR2 influences DNA repair pathway choice and chromatin accessibility.
• CCAR2 regulates transcription, circadian rhythm, metabolism, and NF-kB signaling.
• CCAR2's expression is deregulated in tumors, with conflicting evidence regarding its oncogenic or tumor-suppressive roles.

Conclusions:

• CCAR2 is a critical regulator of the DNA damage response through SIRT1 and p53 pathways.
• CCAR2 exhibits diverse functions in normal cellular processes, including transcription, circadian rhythm, and metabolism.
• The role of CCAR2 in cancer is complex and context-dependent, requiring further investigation.