Cep55 regulates embryonic growth and development by promoting Akt stability in zebrafish

Jeffery, Jessie, Neyt, Christine, Moore, Wade, Paterson, Scott, Bower, Neil I., Chenevix-Trench, Georgia, Verkade, Heather, Hogan, Benjamin M. and Khanna, Kum Kum (2015) Cep55 regulates embryonic growth and development by promoting Akt stability in zebrafish. The FASEB Journal, 29 5: 1999-2009. doi:10.1096/fj.14-265090

Author Jeffery, Jessie
Neyt, Christine
Moore, Wade
Paterson, Scott
Bower, Neil I.
Chenevix-Trench, Georgia
Verkade, Heather
Hogan, Benjamin M.
Khanna, Kum Kum
Title Cep55 regulates embryonic growth and development by promoting Akt stability in zebrafish
Journal name The FASEB Journal   Check publisher's open access policy
ISSN 0892-6638
Publication date 2015-05
Year available 2015
Sub-type Article (original research)
DOI 10.1096/fj.14-265090
Volume 29
Issue 5
Start page 1999
End page 2009
Total pages 11
Place of publication Bethesda, MD United States
Publisher Federation of American Societies for Experimental Biology
Collection year 2016
Language eng
Abstract 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.
Keyword Apoptosis
PI3K/AKT pathway
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
Institute for Molecular Bioscience - Publications
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