Abstract
Pontin (RUVBL1, TIP49, TIP49a, Rvb1) and Reptin (RUVBL2, TIP48, TIP49b, Rvb2) are highly conserved ATPases of the AAA+ (ATPases Associated with various cellular Activities) superfamily and are involved in various cellular processes that are important for oncogenesis. First identified as being upregulated in hepatocellular carcinoma and colorectal cancer, their overexpression has since been shown in multiple cancer types such as breast, lung, gastric, esophageal, pancreatic, kidney, bladder as well as lymphatic, and leukemic cancers. However, their exact functions are still quite unknown as they interact with many molecular complexes with vastly different downstream effectors. Within the nucleus, Pontin and Reptin participate in the TIP60 and INO80 complexes important for chromatin remodeling. Although not transcription factors themselves, Pontin and Reptin modulate the transcriptional activities of bona fide proto-oncogenes such as MYC and β-catenin. They associate with proteins involved in DNA damage repair such as PIKK complexes as well as with the core complex of Fanconi anemia pathway. They have also been shown to be important for cell cycle progression, being involved in assembly of telomerase, mitotic spindle, RNA polymerase II, and snoRNPs. When the two ATPases localize to the cytoplasm, they were reported to promote cancer cell invasion and metastasis. Due to their various roles in carcinogenesis, it is not surprising that Pontin and Reptin are proving to be important biomarkers for diagnosis and prognosis of various cancers. They are also current targets for the development of new therapeutic anticancer drugs.
Highlights
Pontin (RUVBL1, TIP49, TIP49a, Rvb1) and Reptin (RUVBL2, TIP48, TIP49b, Rvb2) belong to the AAA+ (ATPases Associated with various cellular Activities) superfamily whose proteins are characterized by having the conserved Walker A and Walker B motifs, which are involved in ATP binding and hydrolysis (Grigoletto et al, 2011; Matias et al, 2015)
The Role of Pontin/Reptin in TIP60 Histone Acetyl Transferase Activity Histone acetylation is an important strategy for the regulation of gene expression as it typically relaxes chromatin structure allowing the binding of the transcriptional machinery to proper promoter regions (Desjarlais and Tummino, 2016)
Consistent with the overexpression of Pontin and Reptin in many cancer types, the two AAA+ proteins are found to regulate many fundamental cellular pathways involved in cell proliferation and survival
Summary
Pontin (RUVBL1, TIP49, TIP49a, Rvb1) and Reptin (RUVBL2, TIP48, TIP49b, Rvb2) belong to the AAA+ (ATPases Associated with various cellular Activities) superfamily whose proteins are characterized by having the conserved Walker A and Walker B motifs, which are involved in ATP binding and hydrolysis (Grigoletto et al, 2011; Matias et al, 2015). The Role of Pontin/Reptin in TIP60 Histone Acetyl Transferase Activity Histone acetylation is an important strategy for the regulation of gene expression as it typically relaxes chromatin structure allowing the binding of the transcriptional machinery to proper promoter regions (Desjarlais and Tummino, 2016). Role in MYC Regulation MYC is an oncogenic transcription factor that promotes cell proliferation by transcriptionally activating genes involved in cell cycle progression, protein synthesis, and ribosome biogenesis, including Pontin and Reptin (Dang, 2012).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
