演題抄録

一般演題(示説)

開催概要
開催回
第52回・2014年・横浜
 

APC/C plays a role in ubiquitin-mediated turnover of p63

演題番号 : P123-4

[筆頭演者]
Rokudai Susumu:1,2 
[共同演者]
Christiano Angela:3、Prives Carol:2、Nishiyama Masahiko:1

1:Molecular Pharmacology and Oncology, Graduate School of Medicine, Gunma University、2:Biological Sciences, Columbia University、3:Medical Center, Columbia University

 

p63 is identified as cancer stem cell (CSC) marker in squamous cell carcinoma (SqCC) and plays a pivotal role in epithelial development and morphogenesis. The ΔN isoforms of p63 are thought to be involved in both basal-epidermal gene expression and maintenance of epithelial progenitor proliferative potential. It is also thought that ΔN versions of p63 and p73 can serve to inhibit the abilities of their TA isoform counterparts to induce cell cycle arrest and apoptosis. Consistent with this, after DNA damage, while levels of p53 and TAp73 are increased, ΔNp63 proteins are quickly downregulated. To investigate how ΔNp63 is regulated in both normal and stress conditions, we sought to identify novel ΔNp63α proteins interacting with ΔNp63 expressed in human keratinocyte HaCaT cells. Using MALDI-TOF mass spectrometry analysis 20 ΔNp63α-associated polypeptides were identified, including three components of the APC/C ubiquitin ligase complex. We confirmed that these subunits and other APC/C-associated proteins could interact with ΔNp63α using immunoprecipitation-immunoblotting analysis. Ectopic expression of the APC/C activators Cdc20 and Cdh1 led to reduced half-life of ΔNp63α when compared to ΔNp63α expressed alone. In addition, the proteasome inhibitor MG132 suppressed degradation of ΔNp63α mediated by either Cdc20 or Cdh1. Taken together, our data suggest that the APC/C-Cdc20 complex plays a role in ubiquitin-mediated turnover of ΔNp63α. Furthermore, Stxbp4, which we previously reported stabilizes ΔNp63 from Rack1-VHL complex (Li et al., Mol Cell Biol 2000), also suppresses the degradation of ΔNp63α by the APC/C complex. Immunohistochemistry of human skin epidermis showed that Stxbp4 is expressed highly in basal layer and colocalizes with ΔNp63α. These results suggest that Stxbp4 stabilizes ΔNp63α in epidermal layer and may be involved along with ΔNp63α in proliferation, differentiation and stemness in epidermal development.

キーワード

臓器別:その他

手法別:トランスレーショナルリサーチ

前へ戻る