New perspectives on retinoblastoma family functions in differentiation

Cell differentiation is a coordinated process Mat includes cell cycle exit and the expression of unique genes to specify tissue identity. The focus of this review is the recent progress in understanding the functions of the r etinoblastoma (RB) family (RB, p130, p107) in cell differentiation. Much wo rk has focused on the functions of RE in G1 regulation. However, much evide nce now suggests a diverse function in differentiation. For discussion, dif ferentiation is divided into three general steps: cell cycle exit, apoptosi s protection, and tissue-specific gene expression. These processes are coor dinated to provide the final and unique tissue characteristics, The RE fami ly and targets such as E2F and HBP1 have functions in each step. While ther e is much knowledge on each separate step of differentiation, the mechanism s that coordinate cell cycle and tissue-specific events are still not known . New evidence suggests that this coordination contains both positive and n egative regulation of tissue-specific gene expression. RB, p130, HBP1, and other proteins appear to have unexpected functions in regulating tissue-spe cific gene expression. The ubiquitous expressions of these proteins suggest membership in a new and general pathway to coordinate cell cycle events wi th tissue-specific gene expression during differentiation. The collective o bservations hypothesize the existence of a differentiation checkpoint to in sure fidelity.