14-3-3 proteins and the p53 family : a study in keratinocytes

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14-3-3 proteins and the p53 family : a study in keratinocytes

Type: Doctoral Thesis
Title: 14-3-3 proteins and the p53 family : a study in keratinocytes
Author: Niemantsverdriet, Maarten
Publisher: Department of Molecular Genetics, Faculty of Science, Leiden University
Issue Date: 2008-04-24
Keywords: 14-3-3
Apoptosis
Cancer
p53 family
Abstract: Several associations between 14-3-3 proteins and members of the p53 family have been revealed. However, numerous questions regarding 14-3-3 proteins, p53 family members and the relationships between thetwo families remain. This thesis contributes to answer these questions. Downregulation of 14-3-3ζ increased the propensity for DNA-damage induced apoptosis and increased cell-cell contacts, two characteristics that are often lost in cancer cells. Differences between 14-3-3σ and 14-3-3ζ in nucleocytoplasmic shuttling have been described. The difference innucleocytoplasmic shuttling likely forms a basis for specialized biological functions of the 14-3-3 isoforms. Keratinocyte specific p53 regulated G2cell-cycle arrest and the lack of a contribution for 14-3-3σ in this cell-type has been observed, whereas 14-3-3σ induction clearly plays a distinct role in G2 arrest in other cell-types. An improved method for detecting p53 induced apoptosis by flow cytometry is portrayed by expressing a duplicated GFP protein. This double GFP protein can be used for future research in the fields of 14-3-3 and p53. A widely used method to detect and quantify p73 splice-variant expression is critically assessed. It turns out that, using this method it is not possible to accurately quantify p73splice-variants.
Description: Promotor: J. Brouwer, Co-promotor: C. Backendorf
With summary in Dutch
Faculty: Faculteit der Wiskunde en Natuurwetenschappen
Citation: Niemantsverdriet, M., 2008, Doctoral thesis, Leiden University
Sponsor: Tebu-bio Nederland Leids Universiteits Fonds BD Biosciences Nederland
Handle: http://hdl.handle.net/1887/12834
 

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