Factors regulating nuclear localization of MIER1 alpha isoforms

Hand, Aimee M. (2014) Factors regulating nuclear localization of MIER1 alpha isoforms. Masters thesis, Memorial University of Newfoundland.

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Abstract

Mesoderm induction early response 1 (MIER1) gene is located on human chromosome 1p31.2 and encodes a nuclear protein. MIER1 encodes four distinct proteins with a common internal sequence and variable N- and C-termini. MIER1α, the α C-terminus with 23 amino acids and an LXXLL motif for interaction with nuclear hormone receptors, interacts with the estrogen receptor alpha (ERα) in vivo and decreases growth of T47D cells. This study investigated the effect of MIER1α on proliferation and/or survival of human breast adenocarcinoma cells, MCF7, and T47D cells, and the results demonstrated that MIER1α had no effect on cell number. Previous work has revealed that the subcellular localization of MIER1α changes, and loss of nuclear MIER1α might contribute to the advancement of breast cancer. A third isoform arises at the N-terminus, MIER1-3Aα, and contains a leucine-rich nuclear export signal. Inclusion of this exon in MIER1α, to produce MIER1-3Aα, changes its subcellular localization from nuclear to cytoplasmic. It has been shown that the percentage of cells appearing with nuclear MIER1α is different in MCF7 and T47D cells at 78.9 % and 9.2 %, respectively. These two cell lines are cultured under different serum conditions and therefore, the effect of factors in serum on nuclear localization was investigated. Serum was shown to have an appeared effect on nuclear localization of MIER1 isoforms in MCF7 cells, and MIER1α in T47D cells. To investigate the effect of an extracellular growth factor on localization, insulin was added to the cell culture medium. Insulin was shown to have an appeared effect on localization of MIER1α in MCF7 cells. Our results demonstrate that factors in serum may be important to control the nuclear localization of proteins.

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