CLONING OF THE MOUSE BTG3 GENE AND DEFINITION OF A NEW GENE FAMILY (THE BTG FAMILY) INVOLVED IN THE NEGATIVE CONTROL OF THE CELL-CYCLE

It is well known that loss of tumor suppressor genes and more generall y of antiproliferative genes plays a key role in the development of mo st tumors. We report here the cloning of the mouse BTG3 gene and show that its human counterpart maps on chromosome 21. This evolutionarily conserved gene codes for a 30 kDa protein and is expressed in most adu lt murine and human tissues analyzed. However, we demonstrate that its expression is cell cycle dependent and peaks at the end of the G(1) p hase. This gene is homologous to the human BTG1, BTG2 and TOB genes wh ich were demonstrated to act as inhibitors of cell proliferation. Its description allowed us to define better this seven gene family (the BT G gene family) at the structural level and to speculate about its phys iological role in normal and tumoral cells. This family is mainly char acterized by the presence of two conserved domains (BTG boxes A and B) of as yet undetermined function which are separated by a nonconserved 20-25 amino acid sequence.