The retinoblastoma-like protein p130 is involved in the determination of reserve-cells in differentiating myoblasts

During skeletal muscle differentiation, a subset of myoblasts remains quies cent and undifferentiated but retains the capacity to self renew and give r ise to differentiating myoblasts [1-3]: this sub-population of muscle cells was recently termed 'reserve cells' [3]. In order to characterise genes th at can regulate the ratio between reserve cells and differentiating myoblas ts, we examined members of the retinoblastoma tumor suppressor family - Rb, p107 and p130 - an important family of negative regulators of E2F transcri ption factors and cell cycle progression [4]. Although pRb and p107 positiv ely regulate muscle cell differentiation [5-7], the role of p130 in muscle cells remains unknown. We show here that p130 (protein and mRNA), but neith er pRb nor p107, preferentially accumulates during muscle differentiation i n reserve cells. Also, p130 is the major Rb-family protein present in E2F c omplexes in this sub-population of cells. Although forced expression of eit her p130 or pRb in mouse C2 myoblasts efficiently blocked cell cycle progre ssion, only p130 inhibited the differentiation program. Furthermore, muscle cells overexpressing p130 had reduced levels of the muscle promoting facto r MyoD. In addition, p130 repressed the transactivation capacity of MyoD, a n effect abolished by co-transfection of pRb, Thus, we propose that p130, b y blocking cell cycle progression and differentiation, could be part of a s pecific pathway that defines a pool of reserve cells during terminal differ entiation.