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

Sushil Devkota, Young Hoon Sung, Jung Min Choi, Jaehoon Lee, Na Young Ha, Hyunki Kim, ByoungChul Cho, Jaewhan Song, Han Woong Lee

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 PKCα via 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.

Original languageEnglish
Pages (from-to)1887-1896
Number of pages10
JournalInternational Journal of Biochemistry and Cell Biology
Volume44
Issue number11
DOIs
Publication statusPublished - 2012 Nov 1

Fingerprint

Etoposide
Protein Kinase C
Skin
Carcinogenesis
Genes
erbB-1 Genes
9,10-Dimethyl-1,2-benzanthracene
Ubiquitin-Protein Ligases
p53 Genes
Autophagy
Skin Neoplasms
Knockout Mice
Transcriptional Activation
Tumors
Databases
Apoptosis
Breast Neoplasms
Amino Acids
Membranes
Degradation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

Cite this

Devkota, Sushil ; Sung, Young Hoon ; Choi, Jung Min ; Lee, Jaehoon ; Ha, Na Young ; Kim, Hyunki ; Cho, ByoungChul ; Song, Jaewhan ; Lee, Han Woong. / Ei24-deficiency attenuates protein kinase Cα signaling and skin carcinogenesis in mice. In: International Journal of Biochemistry and Cell Biology. 2012 ; Vol. 44, No. 11. pp. 1887-1896.
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Ei24-deficiency attenuates protein kinase Cα signaling and skin carcinogenesis in mice. / Devkota, Sushil; Sung, Young Hoon; Choi, Jung Min; Lee, Jaehoon; Ha, Na Young; Kim, Hyunki; Cho, ByoungChul; Song, Jaewhan; Lee, Han Woong.

In: International Journal of Biochemistry and Cell Biology, Vol. 44, No. 11, 01.11.2012, p. 1887-1896.

Research output: Contribution to journalArticle

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