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Characterization of the functional domains of High Mobility Group A1 (HMGA1)
Author(s) -
Pace Kelly,
Sumter Takita Felder
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.782.21
Subject(s) - high mobility group , neoplastic transformation , transformation (genetics) , biology , gene isoform , microbiology and biotechnology , chemistry , gene , genetics , carcinogenesis
The High Mobility Group A1 (HMGA1) gene encodes for two protein isoforms, HMGA1a and HMGA1b, produced by alternative splicing of hmga1. Expression of HMGA1 causes cell growth and division, however, when overexpressed HMGA1 is implicated in transformation and metastasis. HMGA1 acts by binding to AT rich regions of the minor grooves of DNA, but its specific mechanism of initiating neoplastic transformation is still unknown. To study this, we have focused on the structural components of HMGA1, which has three AT hook DNA binding domains. We are examining how deletions of one or more of these binding domains affect the ability of HMGA1 to cause transformation. Previous studies by our lab identify the second and third binding domains are important regions for transformation. In order to further analyze the domains, we characterized a new construct which allows inducible expression of the protein. The construct produces HMGA1 fused to an estrogen receptor subunit. When cells expressing this protein are treated with an estrogen derivative, 4‐hydroxytamoxifen, HMGA1 is translocated into the nucleus where it is active. In addition, induction of HMGA1‐ER expression promotes the transformed phenotype. This construct should be useful in future characterization studies of the AT hook DNA binding domains of HMGA1. This research is supported by grants from the NIH(P20RR04006) and NSF(0542242).