Recent advances in the understanding of the role and mechanism of CCAR2 in cancer oncology cancer disease health
By Neha MathurAug 4 2023Reviewed by Sophia Coveney In a recent review published in Experimental & Molecular Medicine, researchers described the dual role of cell cycle and apoptosis regulator 2 , a nuclear multidomain protein with six functional domains, in cancer progression as a tumor suppressor and promoter.
Background Previous studies postulated that CCAR2 is a potential tumor suppressor because it stimulated cellular apoptosis by activating and stabilizing p53, the most frequently mutated gene in human cancers. Due to their highly structured nature, all these functional domains exhibited limited flexibility. Nonetheless, these govern all CCAR2 functions and interactions with proteins involved in cellular processes such as transcription, epigenetic regulation, apoptosis, DNA repair, metabolism, and circadian rhythms.
Thus, CCAR2 mutations inducing resistance to apoptosis promotes tumor growth and progression. Two other studies identified CCAR2 as a SIRT1-binding protein whose interaction inhibited the latter's deacetylase activity and promoted p53 and forkhead box O3 acetylation after DNA damage. FOXO3 is a gene-encoding protein associated with aging and rhabdomyosarcoma.
Its interaction with diverse proteins, including those encoded by well-recognized proto-oncogenes, e.g., Erα/β, and oncogenic TFs, such as c-Myc, explain the complex CCAR2 roles in tumorigenesis.
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