Macroscopic Differences in HMGA Oncoproteins Post-Translational Modifications: C-Terminal Phosphorylation of HMGA2 Affects Its DNA Binding Properties

HMGA is a family of nuclear proteins involved in a huge number of functions at the chromatin level. It consists of three members, HMGA1a, HMGA1b, and HMGA2, having high sequence homology and sharing the same structural organization (three highly conserved DNA-binding domains, an acidic C-terminal ta...

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Bibliographic Details
Published in:	Journal of proteome research 2009-06, Vol.8 (6), p.2978-2989
Main Authors:	Sgarra, Riccardo, Maurizio, Elisa, Zammitti, Salvina, Lo Sardo, Alessandra, Giancotti, Vincenzo, Manfioletti, Guidalberto
Format:	Article
Language:	eng
Subjects:	Amino Acid Sequence Cell Line, Tumor Chromatography, Liquid HMGA Proteins - chemistry HMGA Proteins - genetics HMGA Proteins - metabolism HMGA2 Protein - chemistry HMGA2 Protein - genetics HMGA2 Protein - metabolism HMGN Proteins - chemistry HMGN Proteins - genetics HMGN Proteins - metabolism Humans Mass Spectrometry Methylation Molecular Sequence Data Neoplasms - metabolism Phosphorylation Protein Binding Protein Interaction Mapping Protein Processing, Post-Translational Sequence Alignment Serine - metabolism
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Summary:	HMGA is a family of nuclear proteins involved in a huge number of functions at the chromatin level. It consists of three members, HMGA1a, HMGA1b, and HMGA2, having high sequence homology and sharing the same structural organization (three highly conserved DNA-binding domains, an acidic C-terminal tail, and a protein−protein interaction domain). They are considered important nodes in the chromatin context, establishing a complex network of interactions with both promoter/enhancer sequences and nuclear factors. They are involved in a plethora of biological processes and their activities are finely tuned by several different post-translational modifications. We have performed an LC/MS screening on several different cell lines to investigate HMGA proteins expression and their post-translational modifications in order to detect distinctive modification patterns for each. Our analyses evidenced relevant macroscopic differences in the phosphorylation and methylation patterns of these proteins. These differences occur both within the HMGA family members and in the different cell types. Focusing on HMGA2, we have mapped its in vivo phosphorylation sites demonstrating that, similarly to the HMGA1 proteins, it is highly phosphorylated on the acidic C-terminal tail and that these modifications affect its DNA binding properties.
ISSN:	1535-3893 1535-3907