Dynamic and Differential in vivo Modifications of the Isoform HMGA1a and HMGA1b Chromatin Proteins
Most naturally occurring mammalian cancers and immortalized tissue culture cell lines share a common characteristic, the over-expression of full-length high mobility group A1 (HMGA1) proteins. The HMGA1 proto-oncogene codes for two closely related isoform proteins, HMGA1a and HMGA1b, and causes cancerous cellular transformation when over-expressed in either transgenic mice or ''normal'' cultured cell lines. Previous work has suggested that the in vivo types and patterns of the HMGA1 post-translational modifications (PTMs) differ between normal and malignant cells. The present study focuses on the important question of whether HMGA1a and HMGA1b proteins isolated from the same cell type have identical or different PTM patterns and also whether these isoform patterns differ between non-malignant and malignant cells. Two independent mass spectrometry methods were used to identify the types of PTMs found on specific amino acid residues on the endogenous HMGA1a and HMGA1b proteins isolated from a non-metastatic, human mammary epithelial cell line, MCF-7, and a malignant, metastatic cell line derived from MCF-7 cells that over-expressed transgenic HMGA1a protein. While some of the PTMs were the same on both the HMGA1a and HMGA1b proteins isolated from a given cell type, many other modifications were present on one but not the other isoform. Furthermore, we demonstrate that both HMGA1 isoforms are dimethylated on arginine and lysine residues. Most importantly, however, the PTM patterns on the endogenous HMGA1a and HMGA1b proteins isolated from nonmetastatic and metastatic cells were consistently different, suggesting that the isoforms likely exhibit differences in their biological functions/activities in these cell types.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
- Sponsoring Organization:
- US Department of Energy (US)
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 15016142
- Report Number(s):
- PNNL-SA-43483; 3523; KP1102020; TRN: US200510%%98
- Journal Information:
- Journal of Biological Chemistry, Vol. 280, Issue 10; Other Information: PBD: 1 Mar 2005
- Country of Publication:
- United States
- Language:
- English
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