The gene PC3(TIS21/BTG2), prototype member of the PC3/BTG/TOB family: Regulator in control of cell growth, differentiation, and DNA repair?

PC3(TIS21/BTG2) is the founding member of a family of genes endowed with an tiproliferative properties, namely BTG1, ANA/BTG3, PC3B, TOE, and TOB2. PC3 was originally isolated as a gene induced by nerve growth factor during ne uronal differentiation of rat PC12 cells, or by TPA in NIH3T3 cells (named TIS21), and is a marker for neuronal birth in vivo. This and other findings suggested its implication in the process of neurogenesis as mediator of th e growth arrest before differentiation. Remarkably, its human homolog, name d BTG2, was shown to be p53-inducible, in conditions of genotoxic damage. p C3(TIS21/BTG2) impairs G(1)-S progression, either by a Rb-dependent pathway through inhibition of cyclin D1 transcription, or in a Rb-independent fash ion by cyclin E downregulation. pC3(TIS21/BTG2) might also control the Ct c heckpoint. Furthermore, pC3(TIS21/BTG2) interacts with carbon catabolite re pressor protein-associated factor 1 (CAF-1), a molecule that associates to the yeast transcriptional complex CCR4 and might influence cell cycle, with the transcription factor Hoxb9, and with the protein-arginine methyltransf erase 1, that might control transcription through histone methylation. Curr ent evidence suggests a physiological role of PC3(TIS21/BTG2) in the contro l of cell cycle arrest following DNA damage and other types of cellular str ess, or before differentiation of the neuron and other cell types. The mole cular function of pC3(TIS21/BTG2) is still unknown, but its ability to modu late cyclin D1 transcription, or to synergize with the transcription factor Hoxb9, suggests that it behaves as a transcriptional co-regulator. (C) 200 1 Wiley-Liss. Inc.