Cep55 regulates embryonic growth and development by promoting Akt stability in zebrafish
被引:23
作者:
Jeffery, Jessie
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QIMR Berghofer Med Res Inst, Signal Transduct Lab, Brisbane, Qld, AustraliaQIMR Berghofer Med Res Inst, Signal Transduct Lab, Brisbane, Qld, Australia
Jeffery, Jessie
[1
]
Neyt, Christine
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机构:
Univ Queensland, Inst Mol Biosci, Vasc Biol & Dev Lab, Brisbane, Qld, AustraliaQIMR Berghofer Med Res Inst, Signal Transduct Lab, Brisbane, Qld, Australia
Neyt, Christine
[2
]
Moore, Wade
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机构:
Monash Univ, Zebrafish Dev Genet Lab, Clayton, Vic, AustraliaQIMR Berghofer Med Res Inst, Signal Transduct Lab, Brisbane, Qld, Australia
Moore, Wade
[3
]
Paterson, Scott
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Univ Queensland, Inst Mol Biosci, Vasc Biol & Dev Lab, Brisbane, Qld, AustraliaQIMR Berghofer Med Res Inst, Signal Transduct Lab, Brisbane, Qld, Australia
Paterson, Scott
[2
]
Bower, Neil I.
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Univ Queensland, Inst Mol Biosci, Vasc Biol & Dev Lab, Brisbane, Qld, AustraliaQIMR Berghofer Med Res Inst, Signal Transduct Lab, Brisbane, Qld, Australia
Bower, Neil I.
[2
]
Chenevix-Trench, Georgia
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QIMR Berghofer Med Res Inst, Canc Genet Lab, Brisbane, Qld, AustraliaQIMR Berghofer Med Res Inst, Signal Transduct Lab, Brisbane, Qld, Australia
Chenevix-Trench, Georgia
[4
]
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Verkade, Heather
[3
]
Hogan, Benjamin M.
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机构:
Univ Queensland, Inst Mol Biosci, Vasc Biol & Dev Lab, Brisbane, Qld, AustraliaQIMR Berghofer Med Res Inst, Signal Transduct Lab, Brisbane, Qld, Australia
Hogan, Benjamin M.
[2
]
Khanna, Kum Kum
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QIMR Berghofer Med Res Inst, Signal Transduct Lab, Brisbane, Qld, AustraliaQIMR Berghofer Med Res Inst, Signal Transduct Lab, Brisbane, Qld, Australia
Khanna, Kum Kum
[1
]
机构:
[1] QIMR Berghofer Med Res Inst, Signal Transduct Lab, Brisbane, Qld, Australia
[2] Univ Queensland, Inst Mol Biosci, Vasc Biol & Dev Lab, Brisbane, Qld, Australia
[3] Monash Univ, Zebrafish Dev Genet Lab, Clayton, Vic, Australia
[4] QIMR Berghofer Med Res Inst, Canc Genet Lab, Brisbane, Qld, Australia
CEP55 was initially described as a centrosome- and midbody-associated protein and a key mediator of cytokinesis. More recently, it has been implicated in PI3K/AKT pathway activation via an interaction with the catalytic subunit of PI3K. However, its role in embryonic development is unknown. Here we describe a cep55 nonsense mutant zebrafish with which we can study the in vivo physiologic role of Cep55. Homozygous mutants underwent extensive apoptosis by 24 hours postfertilization (hpf) concomitant with cell cycle defects, and heterozygous carriers were indistinguishable from their wild-type siblings. A similar phenotype was also observed in zebrafish injected with a cep55 morpholino, suggesting the mutant is a cep55 loss-of-function model. Further analysis revealed that Akt was destabilized in the homozygous mutants, which partially phenocopied Akt1 and Akt2 knockdown. Expression of either constitutively activated PIK3CA or AKT1 could partially rescue the homozygous mutants. Consistent with a role for Cep55 in regulation of Akt stability, treatment with proteasome inhibitor, MG132, partially rescued the homozygous mutants. Taken together, these results provide the first description of Cep55 in development and underline the importance of Cep55 in the regulation of Pi3k/Akt pathway and in particular Akt stability.
机构:
Chang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Chen, Chang-Han
;
Lai, Jin-Mei
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Fu Jen Catholic Univ, Dept Life Sci, Taipei, Hsien, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Lai, Jin-Mei
;
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Chou, Teh-Ying
;
Chen, Cheng-Yu
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Natl Yang Ming Univ, Inst Clin Med, Taipei, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Chen, Cheng-Yu
;
Su, Li-Jen
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Taipei Vet Gen Hosp, Dept Surg, Div Thorac Surg, Taipei, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Su, Li-Jen
;
Lee, Yuan-Chii
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机构:
Taipei Med Univ, Grad Inst Med Informat, Taipei, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Lee, Yuan-Chii
;
Cheng, Tai-Shan
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机构:
Kaohsiung Med Univ, Grad Inst Biochem, Kaohsiung, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Cheng, Tai-Shan
;
Hong, Yi-Ren
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Kaohsiung Med Univ, Grad Inst Biochem, Kaohsiung, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Hong, Yi-Ren
;
Chou, Chen-Kung
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机构:
Chang Gung Univ, Dept Life Sci, Tao Yuan, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Chou, Chen-Kung
;
Whang-Peng, Jacqueline
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Wan Fang Hosp, Div Canc Ctr, Taipei, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Whang-Peng, Jacqueline
;
Wu, Yu-Chung
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Taipei Vet Gen Hosp, Dept Surg, Div Thorac Surg, Taipei, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Wu, Yu-Chung
;
Huang, Chi-Ying F.
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机构:
Natl Yang Ming Univ, Inst Clin Med, Taipei, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
机构:
Chang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Chen, Chang-Han
;
Lai, Jin-Mei
论文数: 0引用数: 0
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机构:
Fu Jen Catholic Univ, Dept Life Sci, Taipei, Hsien, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Lai, Jin-Mei
;
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机构:
Chou, Teh-Ying
;
Chen, Cheng-Yu
论文数: 0引用数: 0
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机构:
Natl Yang Ming Univ, Inst Clin Med, Taipei, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Chen, Cheng-Yu
;
Su, Li-Jen
论文数: 0引用数: 0
h-index: 0
机构:
Taipei Vet Gen Hosp, Dept Surg, Div Thorac Surg, Taipei, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Su, Li-Jen
;
Lee, Yuan-Chii
论文数: 0引用数: 0
h-index: 0
机构:
Taipei Med Univ, Grad Inst Med Informat, Taipei, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Lee, Yuan-Chii
;
Cheng, Tai-Shan
论文数: 0引用数: 0
h-index: 0
机构:
Kaohsiung Med Univ, Grad Inst Biochem, Kaohsiung, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Cheng, Tai-Shan
;
Hong, Yi-Ren
论文数: 0引用数: 0
h-index: 0
机构:
Kaohsiung Med Univ, Grad Inst Biochem, Kaohsiung, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Hong, Yi-Ren
;
Chou, Chen-Kung
论文数: 0引用数: 0
h-index: 0
机构:
Chang Gung Univ, Dept Life Sci, Tao Yuan, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Chou, Chen-Kung
;
Whang-Peng, Jacqueline
论文数: 0引用数: 0
h-index: 0
机构:
Wan Fang Hosp, Div Canc Ctr, Taipei, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Whang-Peng, Jacqueline
;
Wu, Yu-Chung
论文数: 0引用数: 0
h-index: 0
机构:
Taipei Vet Gen Hosp, Dept Surg, Div Thorac Surg, Taipei, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan
Wu, Yu-Chung
;
Huang, Chi-Ying F.
论文数: 0引用数: 0
h-index: 0
机构:
Natl Yang Ming Univ, Inst Clin Med, Taipei, TaiwanChang Gung Univ, Coll Med, Chang Gung Mem Hospital, Kaohsiung Med Ctr,Dept Otolaryngol, Kaohsiung, Taiwan