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  • Original Paper
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Metastatic tumor antigen 1 short form (MTA1s) associates with casein kinase I-γ2, an estrogen-responsive kinase

Oncogene volume 23, pages 4422–4429 (2004)Cite this article

Abstract

Recent studies have shown that metastasis-associated protein-1 short form (MTA1s) – metastatic tumor antigen 1 short form sequesters estrogen receptor-alpha (ER-α) in the cytoplasm of breast cancer cells. Using a yeast two-hybrid screening to clone MTA1s-interacting proteins, we identified casein kinase I-gamma 2 (CKI-γ2, a ubiquitously expressed cytoplasmic kinase) as an MTA1s-binding protein. We show that MTA1s interacts with CKI-γ2 both in vitro and in vivo and colocalizes in the cytoplasm. In addition, we found that CKI-γ2 can phosphorylate MTA1s, but not ER, in an antiestrogen-dependent manner and that estrogen stimulates CKI-γ2 activity that could be effectively blocked by a specific inhibitor of CKI. CKI-γ2 could further potentiate the ER corepressive function of MTA1s. Kinase dead CK1-γ2 could not repress estrogen-induced ER transactivation functions. Results from mutagenesis studies suggest that substitution of the serine residue at 321 to alanine, which is a possible CKI-γ2 phopshorylation site in MTA1s, results in a significant reduction in the ability of MTA1s to repress ER transactivation. These findings identified MTA1s as a target of CKI-γ2, and provided new evidence to suggest that CKI-γ2 phosphorylates and modulates the functions of MTA1s, and that these extranuclear effects of estrogen might have important implications in regulating the functions of MTA1s in human mammary epithelial and cancer cells.

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Abbreviations

ER:

estrogen receptor-alpha

ERE:

estrogen response element

NR:

nuclear receptor

MTA1s:

metastasis-associated protein-1 short form

E2:

17-β-estrodiol

AF domain:

activation function domain

luc:

luciferase

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Acknowledgements

This study was supported in part by NIH Grants CA098823 and CA90970 and Susan G. Komen Foundation Grant BCRT 2000835 (to R.K).

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Authors and Affiliations

  1. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA

    Sandip K Mishra, Zhibo Yang, Abhijit Mazumdar, Amjad H Talukder & Rakesh Kumar

  2. Department of Experimental Medicine, McGill University, Montreal, H3A 2B2, Quebec, Canada

    Louise Larose

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  1. Sandip K Mishra
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Correspondence to Rakesh Kumar.

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Mishra, S., Yang, Z., Mazumdar, A. et al. Metastatic tumor antigen 1 short form (MTA1s) associates with casein kinase I-γ2, an estrogen-responsive kinase. Oncogene 23, 4422–4429 (2004). https://doi.org/10.1038/sj.onc.1207569

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