HMGA1 protein is a novel target of the ATM kinase

Abstract

The high mobility group HMGA1 protein belongs to a family of architectural factors that play a role in chromosomal organisation and gene transcription regulation. HMGA1 overexpression represents a common feature of human malignant tumours and is causally associated with neoplastic transformation and metastatic progression. Recently, HMGA1 expression has been correlated with the presence of chromosomal rearrangements and suggested to promote genomic instability. Here, we report a novel interaction between HMGA1 protein and the ataxia-telangiectasia mutated (ATM) kinase, the major key player in the cellular response to DNA damage caused by several agents such as ionising radiation (IR). We identified an SQ motif on HMGA1, which is effectively phosphorylated by ATM in vitro and in vivo. Interestingly, confocal microscopy revealed that HMGA1 colocalises with the activated form of ATM (ATM S1981p). Moreover, HMGA1 ectopic expression decreases cell survival following exposure to IR as assessed by clonogenic survival in MCF-7 cells, further supporting the hypothesis that HMGA1 might act as a downstream target of the ATM pathway in response to DNA damage.