title: RUVBL2 is a novel repressor of ARF transcription.
abstract: ARF is the second most commonly inactivated tumor suppressor behind p53. It has been implicated in the control of cell proliferation, cell senescence, and tumor suppression. However, the detailed mechanism underlying the transcriptional control of ARF remains largely unknown. Here we report RUVBL2 as a novel transcriptional repressor of ARF. Ectopic expression of RUVBL2 decreases the levels of ARF, whereas knockdown of RUVBL2 results in a marked increase in ARF levels. In addition, RUVBL2 down-regulates the levels of p53 in an ARF-dependent manner. Mechanistically, RUVBL2 binds to the distal region of ARF promoter, thus leading to the repression of ARF transcription. These results suggest an important role of RUVBL2 in the regulation of ARF-p53 pathway.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
authors.forename: Chongwei
authors.initials: C
authors.lastname: Xie
authors.forename: Wenyu
authors.initials: W
authors.lastname: Wang
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Mian
authors.initials: M
authors.lastname: Wu
authors.forename: Yide
authors.initials: Y
authors.lastname: Mei
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004265:DNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C122079:RUVBL2 protein, human; C518330:RUVBL2 protein, mouse