title: Golgi-associated RhoBTB3 targets cyclin E for ubiquitylation and promotes cell cycle progression.
abstract: Cyclin E regulates the cell cycle transition from G1 to S phase and is degraded before entry into G2 phase. Here we show that RhoBTB3, a Golgi-associated, Rho-related ATPase, regulates the S/G2 transition of the cell cycle by targeting cyclin E for ubiquitylation. Depletion of RhoBTB3 arrested cells in S phase, triggered Golgi fragmentation, and elevated cyclin E levels. On the Golgi, RhoBTB3 bound cyclin E as part of a Cullin3 (CUL3)-dependent RING-E3 ubiquitin ligase complex comprised of RhoBTB3, CUL3, and RBX1. Golgi association of this complex was required for its ability to catalyze cyclin E ubiquitylation and allow normal cell cycle progression. These experiments reveal a novel role for a Ras superfamily member in catalyzing cyclin E turnover during S phase, as well as an unexpected, essential role for the Golgi as a ubiquitylation platform for cell cycle control.
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Albert
authors.initials: A
authors.lastname: Lu
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Pfeffer
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D048429:Cell Size; D044842:Cullin Proteins / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000201:enzymology* / Q000473:pathology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D059807:S Phase Cell Cycle Checkpoints; D013997:Time Factors; D014162:Transfection; D054875:Ubiquitination; D014741:Video Recording; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C475820:CCNE1 protein, human; C503645:CUL3 protein, human; D002352:Carrier Proteins; D044842:Cullin Proteins; D019927:Cyclin E; D015513:Oncogene Proteins; C479529:RBX1 protein, human; C541346:RhoBTB3 protein, human; D020741:rho GTP-Binding Proteins