Title of Abstract
Molecular Evaluation of Transformation-Induced Methylation of the High Mobility Group A1 (HMGA1) Chromatin Binding Proteins
Poster Number
09
College
College of Arts and Sciences
Department
Chemistry, Physics, Geology, & the Environment
Faculty Mentor
Takita Sumter, Ph.D.
Abstract
Aberrant expression of high mobility group A1 (hmga1), resulting from inactivating defects in upstream tumor suppressor genes or upregulation of oncogenic transactivators, induces the initiation of cancer progression pathways. The protein products of hmga1, HMGA1a and HMGA1b, are characterized by the presence of three DNA-binding motifs that possess a central RGR sequence that plays a key role in preferential binding to the minor groove of AT-rich stretches of target DNA. Importantly, R25 of the RGR sequence within the first DNA-binding motif bears covalent modifications that may recruit or repel specific transcriptional regulators in cancer cells. Despite the implication of hmga1 and arginine methylation in oncogenic function, the role of epigenetic regulation of hmga1 by arginine methylation has not been evaluated. Here, we investigate the impact of R25 substitutions on HMGA1b binding DNA targets using fluorescence spectroscopy and functional cellular assays. R25 substitutions disrupt DNA binding to various targets and suppress HMGA1-dependent oncogenic transformation. Together, our data reveal new potential anti-cancer strategies by targeting HMGA1 protein methylation and downstream targets.
Start Date
24-4-2015 1:20 PM
End Date
24-4-2015 2:50 PM
Molecular Evaluation of Transformation-Induced Methylation of the High Mobility Group A1 (HMGA1) Chromatin Binding Proteins
Richardson Ballroom
Aberrant expression of high mobility group A1 (hmga1), resulting from inactivating defects in upstream tumor suppressor genes or upregulation of oncogenic transactivators, induces the initiation of cancer progression pathways. The protein products of hmga1, HMGA1a and HMGA1b, are characterized by the presence of three DNA-binding motifs that possess a central RGR sequence that plays a key role in preferential binding to the minor groove of AT-rich stretches of target DNA. Importantly, R25 of the RGR sequence within the first DNA-binding motif bears covalent modifications that may recruit or repel specific transcriptional regulators in cancer cells. Despite the implication of hmga1 and arginine methylation in oncogenic function, the role of epigenetic regulation of hmga1 by arginine methylation has not been evaluated. Here, we investigate the impact of R25 substitutions on HMGA1b binding DNA targets using fluorescence spectroscopy and functional cellular assays. R25 substitutions disrupt DNA binding to various targets and suppress HMGA1-dependent oncogenic transformation. Together, our data reveal new potential anti-cancer strategies by targeting HMGA1 protein methylation and downstream targets.
