MAGEA1 interacts with FBXW7 and regulates ubiquitin ligase-mediated turnover of NICD1 in breast and ovarian cancer cells

J. Zhao, Y. Wang, C. Mu, Yan Xu, J. Sang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Melanoma-associated antigen A1 (MAGEA1) is member of the MAGE gene family that is expressed in male germ line cells and placenta under normal physiological conditions. Although MAGEA1's expression levels have been evaluated as one of the cancer testis (CT) antigens for immunotherapy in melanoma and several other cancers, its functional role and signaling mechanisms are largely unknown. In this study, we examined the functional involvement and signaling mechanisms of MAGEA1 in breast and ovarian cancer cells. Inhibitory effects of MAGEA1 on cell proliferation and migration were observed using both gain-of- (MAGEA1 overexpression) and loss-of- (siRNA interference) function approaches in breast (MCF-7 and MDA-MB-231) and ovarian (SKOV3 and SKOV3ip) cancer cell lines. We revealed a novel interaction between MAGEA1 and the intracellular segment of NOTCH1 receptor (NICD1). MAGEA1 reduced NICD1's stability by promoting the ubiquitin modification of NICD1. MAGEA1 also interacted with FBXW7, subunit of E3 ubiquitin protein ligase complex SCF, and the latter was functionally involved in NICD1 ubiquitination and degradation. In addition, siRNA interference of FBXW7 reversed the inhibitory effect of MAGEA1 on migration and proliferation of MCF-7 and MDA-MB-231 cells. These newly discovered MAGEA1-NICD1 and MAGEA1-FBXW7 interactions have potential clinical implications in breast and ovarian cancer treatment.

Original languageEnglish (US)
Pages (from-to)5023-5034
Number of pages12
JournalOncogene
Volume36
Issue number35
DOIs
StatePublished - Aug 31 2017

Fingerprint

Melanoma-Specific Antigens
Ligases
Ubiquitin
Ovarian Neoplasms
Breast Neoplasms
Ubiquitin-Protein Ligase Complexes
Small Interfering RNA
Ubiquitination
Testicular Neoplasms
Germ Cells
Immunotherapy
Placenta
Cell Movement
Melanoma
Neoplasms
Breast
Cell Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

MAGEA1 interacts with FBXW7 and regulates ubiquitin ligase-mediated turnover of NICD1 in breast and ovarian cancer cells. / Zhao, J.; Wang, Y.; Mu, C.; Xu, Yan; Sang, J.

In: Oncogene, Vol. 36, No. 35, 31.08.2017, p. 5023-5034.

Research output: Contribution to journalArticle

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