Abstract
Simple SummaryRAP1 (TERF2IP) is a member of the shelterin complex that protects telomeric DNA and plays a critical role in maintaining chromosome stability. However, mammalian RAP1 was recently found to have additional functions apart from telomeres, acting as a regulator of the NF-κB pathway and transcription factor, and has been suggested that they have putative roles in cancer development. Here, we focus on the main roles of RAP1 in different mechanisms of oncogenesis, progression, and chemoresistance, and consider the clinical significance of findings about its regulation and biological functions.Mammalian RAP1 (TERF2IP), the most conserved shelterin component, plays a pleiotropic role in the regulation of a variety of cellular processes, including cell metabolism, DNA damage response, and NF-κB signaling, beyond its canonical telomeric role. Moreover, it has been demonstrated to be involved in oncogenesis, progression, and chemoresistance in human cancers. Several mutations and different expression patterns of RAP1 in cancers have been reported. However, the functions and mechanisms of RAP1 in various cancers have not been extensively studied, suggesting the necessity of further investigations. In this review, we summarize the main roles of RAP1 in different mechanisms of cancer development and chemoresistance, with special emphasis on the contribution of RAP1 mutations, expression patterns, and regulation by non-coding RNA, and briefly discuss telomeric and non-telomeric functions.
Highlights
Mammalian telomeres are specialized nucleoprotein complexes, consisting of several kilobases of double-stranded DNA with the hexameric repetetive sequence 5‘-TTAGGG/3‘AATCCC in vertebrates, the telomeric repeat-containing RNA (TERRA), and the specific, telomere-associated shelterin proteins
The RAP1 C-terminal domain (RCT) domain is a three-helix bundle that recognizes a helical peptide from binding partners, such as TRF2 driven by hydrophobic interactions, which tethers it to the telomeres
We found that the expression of RAP1 and POT1 at the protein level was positively correlated with the levels of expression and activity of BCR/ABL1, suggesting that BCR/ABL1 kinase expression and activity may upregulate the levels of RAP1 and POT1 and play a crucial role in the maintenance of telomeres in chronic myeloid leukemia (CML)
Summary
Mammalian telomeres are specialized nucleoprotein complexes, consisting of several kilobases of double-stranded DNA with the hexameric repetetive sequence 5‘-TTAGGG/3‘AATCCC in vertebrates, the telomeric repeat-containing RNA (TERRA), and the specific, telomere-associated shelterin proteins. It is believed that this single-stranded extension plays a crucial role for proper telomere function, potentially by promoting the formation of telomeric T-loop/D-loop structure [1,2] These structures maintain genome integrity by capping the chromosome terminus protecting them from end-to-end fusion, degradation, or recombination [1]. Telomere shortening below a critical level of telomeric sequence repetition leads to cell cycle arrest, and senescence or apoptosis [2] Some cells, such as germ cells, stem cells, or cancer cells, have mechanisms that help maintain the appropriate telomere length. RAP1 ( known as TERF2IP) is a member of the shelterin complex that protects telomeric DNA and plays a critical role in maintaining chromosome stability. We discuss the function of RAP1 in light of already known data about the role of RAP1 in human cancers
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call