TEIF associated centrosome activity is regulated by EGF/PI3K/Akt signaling.
Centrosome amplification, which is a characteristic of cancer cells, has been understood as a driving force of genetic instability in the development of cancer. In previous work, we demonstrated that TEIF (transcriptional element-interacting factor) distributes in the centrosomes and regulates centrosome status under both physiologic and pathologic conditions. Here we identify TEIF as a downstream effector in EGF/PI3K/Akt signaling. The addition of EGF or transfection of active Akt stimulates centrosome TEIF distribution, resulting in an increase of centrosome splitting and amplification, while inhibitors of either PI3K or Akt attenuate these changes in TEIF and the associated centrosome status. A consensus motif for Akt phosphorylation (RHRVLT) proved to be involved in centrosomal TEIF localization, and the 469-threonine of this motif may be phosphorylated by Akt both in vitro and in vivo. Elimination of this phosphorylated site on TEIF caused reduced centrosome distribution and centrosome splitting or amplification. Moreover, TEIF closely co-localized with C-NAP1 at the proximal ends of centrioles, and centriolar loading of TEIF stimulated by EGF/Akt could displace C-NAP1, resulting in centrosome splitting. These findings reveal linkage of the EGF/PI3K/Akt signaling pathway to regulation of centrosome status which may act as an oncogenic pathway and induce genetic instability in carcinogenesis.
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Jing
J
Zhao
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Yongxin
Y
Zou
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Haijing
H
Liu
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Huali
H
Wang
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Hong
H
Zhang
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Wei
W
Hou
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Xin
X
Li
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Xinying
X
Jia
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Jing
J
Zhang
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Lin
L
Hou
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China. Electronic address: zhangbo@bjmu.edu.cn.
Bo
B
Zhang
D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D002460:Cell Line; D002502:Centrioles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018385:Centrosome / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor; D049452:Green Fluorescent Proteins; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D010767:Phosphorylcholine; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; C464929:SCYL1 protein, human; C105905:perifosine
Akt; C-NAP1; Centrosome amplification; EGF