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Ei24-deficiency attenuates protein kinase Cα signaling and skin carcinogenesis in mice.

Authors
 Sushil Devkota  ;  Young Hoon Sung  ;  Jung-Min Choi  ;  Jaehoon Lee  ;  Na Young Ha  ;  Hyunki Kim  ;  Byoung Chul Cho  ;  Jaewhan Song  ;  Han-Woong Lee 
Citation
 INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, Vol.44(11) : 1887-1896, 2012 
Journal Title
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
ISSN
 1357-2725 
Issue Date
2012
MeSH
9,10-Dimethyl-1,2-benzanthracene ; Amino Acid Sequence ; Animals ; Apoptosis Regulatory Proteins/chemistry ; Apoptosis Regulatory Proteins/deficiency* ; Apoptosis Regulatory Proteins/metabolism ; Binding, Competitive ; Cell Transformation, Neoplastic/pathology* ; Clone Cells ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/metabolism* ; Cytoprotection ; Enzyme Stability ; Female ; Humans ; Keratinocytes/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Biological ; Molecular Sequence Data ; Nuclear Proteins/chemistry ; Nuclear Proteins/deficiency* ; Nuclear Proteins/metabolism ; Protein Binding ; Proteolysis ; Receptor, Epidermal Growth Factor/genetics ; Receptor, Epidermal Growth Factor/metabolism ; Signal Transduction* ; Skin Neoplasms/enzymology* ; Skin Neoplasms/pathology* ; Transcriptional Activation/genetics
Keywords
DMBA/TPA skin-carcinogenesis ; EGFR ; Ei24 ; PKCα ; RINCK1
Abstract
Etoposide-induced gene 24 (Ei24) is a p53 target gene that inhibits growth, induces apoptosis and autophagy, as well as suppresses breast cancer. To evaluate the role of Ei24 in in vivo tumorigenesis, we generated an Ei24-deficient mouse model. Here, we report that, although Ei24 homozygous knockout mice are embryonic lethal, Ei24 heterozygous null mice are attenuated to DMBA/TPA-induced carcinogenesis with regard to the number and size of tumors but not the incidence. Ei24 contains a functional consensus motif, named as an R motif that is highly analogous to amino acids 105-110 of RINCK1, an E3 ligase for protein kinase C (PKC) proteins. We found that Ei24 stabilizes PKCαvia RINCK degradation and competition with RINCK for binding with the C1a domain of PKCα. We also found that Ei24 contributes to PKCα-mediated transactivation of EGFR by promoting PKCα membrane localization and interaction with EGFR. Finally, using Oncomine database we show that Ei24 and EGFR are upregulated in some subsets of human HNSCC. These results suggest that Ei24 is a regulator of the RINCK1-PKCα-EGFR signaling pathway in the development of skin-cancer.
Full Text
http://www.sciencedirect.com/science/article/pii/S1357272512002336
DOI
22771957
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90435
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