Steinman R A, Hoffman B, Iro A, Guillouf C, Liebermann D A, el-Houseini M E
Department of Medicine, University of Pittsburgh School of Medicine, PA 15213.
Oncogene. 1994 Nov;9(11):3389-96.
The recently cloned protein, p21 (WAF1/CIP1) is a downstream effector of p53, and mediates growth arrest by inhibiting the action of G1 cyclin-dependent kinases. Since cellular differentiation is frequently characterized by G1 arrest, we examined whether p21 upregulation occurs in differentiation. We show that p21 expression is triggered by multiple differentiation-inducing agents in hematopoietic and hepatoma cells through a p53-independent pathway. The dramatic rise in p21 levels occurs as an immediate early response to differentiation inducers. The induction of p21 is coupled to the expression of early differentiation markers, and is uncoupled from apoptosis. Finally, evidence is presented that p21 expression is uncoupled from G1 arrest in the presence of deregulated c-myc.
最近克隆出的蛋白p21（WAF1/CIP1）是p53的下游效应分子，通过抑制G1期细胞周期蛋白依赖性激酶的活性介导生长停滞。由于细胞分化常常以G1期停滞为特征，我们研究了p21上调是否发生在分化过程中。我们发现，在造血细胞和肝癌细胞中，多种分化诱导剂通过一条不依赖p53的途径触发p21表达。p21水平的显著升高是对分化诱导剂的即时早期反应。p21的诱导与早期分化标志物的表达相关，且与细胞凋亡无关。最后，有证据表明，在c-myc失调的情况下，p21的表达与G1期停滞无关。
