title: AKAP95 promotes cell cycle progression via interactions with cyclin E and low molecular weight cyclin E.
abstract: AKAP95 in lung cancer tissues showed higher expression than in paracancerous tissues. AKAP95 can bind with cyclin D and cyclin E during G1/S cell cycle transition, but its molecular mechanisms remain unclear. To identify the mechanism of AKAP95 in cell cycle progression, we performed AKAP95 transfection and silencing in A549 cells, examined AKAP95, cyclin E1 and cyclin E2 expression, and the interactions of AKAP95 with cyclins E1 and E2. Results showed that over-expression of AKAP95 promoted cell growth and AKAP95 bound cyclin E1 and E2, low molecular weight cyclin E1 (LWM-E1) and LWM-E2. Additionally AKAP95 bound cyclin E1 and LMW-E2 in the nucleus during G1/S transition, bound LMW-E1 during G1, S and G2/M, and bound cyclin E2 mainly on the nuclear membrane during interphase. Cyclin E2 and LMW-E2 were also detected. AKAP95 over-expression increased cyclin E1 and LMW-E2 expression but decreased cyclin E2 levels. Unlike cyclin E1 and LMW-E2 that were nuclear located during the G1, S and G1/S phases, cyclin E2 and LMW-E1 were expressed in all cell cycle phases, with cyclin E2 present in the cytoplasm and nuclear membrane, with traces in the nucleus. LMW-E1 was present in both the cytoplasm and nucleus. The 20 kDa form of LMW-E1 showed only cytoplasmic expression, while the 40 kDa form was nuclear expressed. The expression of AKAP95, cyclin E1, LMW-E1 and -E2, might be regulated by cAMP. We conclude that AKAP95 might promote cell cycle progression by interacting with cyclin E1 and LMW-E2. LMW-E2, but not cyclin E2, might be involved in G1/S transition. The binding of AKAP95 and LMW-E1 was found throughout cell cycle.
authors.affiliation: Department of Gastrointestinal Surgery, Affiliated Zhongshan Hospital of Dalian University Dalian Liaoning, 116001, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University Xiamen Fujian, 361102, China.
authors.forename: Deng-Cheng
authors.initials: DC
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University Xiamen Fujian, 361102, China.
authors.forename: Wen-Xin
authors.initials: WX
authors.lastname: Zhuang
authors.affiliation: Department of Gastrointestinal Surgery, Affiliated Zhongshan Hospital of Dalian University Dalian Liaoning, 116001, China.
authors.forename: Su-Hang
authors.initials: SH
authors.lastname: Hua
authors.affiliation: Department of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University Shenyang Liaoning, 110015, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University Xiamen Fujian, 361102, China.
authors.forename: Yang-Yang
authors.initials: YY
authors.lastname: Yuan
authors.affiliation: Department of Integrated TCM and Western Medicine, Beijing YouAn Hospital Affiliated with Capital Medical University Beijing, 10069, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University Xiamen Fujian, 361102, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University Xiamen Fujian, 361102, China.
authors.forename: Bo-Gang
authors.initials: BG
authors.lastname: Teng
authors.affiliation: The First Affiliated Hospital of Xiamen University Xiamen Fujian, 361102, China.
authors.forename: Xiu-Yi
authors.initials: XY
authors.lastname: Yu
authors.affiliation: Department of Gastrointestinal Surgery, Affiliated Zhongshan Hospital of Dalian University Dalian Liaoning, 116001, China.
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University Xiamen Fujian, 361102, China.
authors.forename: Yong-Xing
authors.initials: YX
authors.lastname: Zhang
keywords: AKAP95; cell cycle; cyclin E; low molecular weight cyclin E; proliferation