Xu H J, Xu K, Zhou Y, Li J, Benedict W F, Hu S X
Center for Biotechnology, Baylor College of Medicine, Woodlands, TX 77381.
Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9837-41. doi: 10.1073/pnas.91.21.9837.
The retinoblastoma (RB) gene encodes a nuclear phosphoprotein of 928 amino acids (pRB). Thus far, much effort in RB research has been focused on both the viral oncoprotein-binding domains and the C-terminal domain, whereas little is known about the N-terminal moiety of the protein. We report here that an N-terminal truncated RB protein of approximately 94 kDa (pRB94) exerts more potent cell growth suppression as compared to the full-length pRB protein in a diversity of tumor cell lines examined, including those having a normal endogenous RB gene. Tumor cells transfected with the pRB94-expressing plasmids displayed multiple morphological changes frequently associated with cellular senescence and/or apoptosis. They failed to enter S phase and rapidly died. The pRB94 expressed in recipient tumor cells had a longer half-life than the full-length pRB protein and tended to remain in an active un- or hypophosphorylated form. Since it has also been found that N-terminal truncated RB proteins often accumulated in growth-arrested and/or differentiated tumor cells, we suggest that N-terminal truncation of pRB may be one of the cellular mechanisms modulating the RB protein function in cell-cycle control.
视网膜母细胞瘤（RB）基因编码一种由928个氨基酸组成的核磷蛋白（pRB）。到目前为止，RB研究的很多精力都集中在病毒癌蛋白结合结构域和C末端结构域上，而对于该蛋白的N末端部分却知之甚少。我们在此报告，在多种检测的肿瘤细胞系中，包括那些具有正常内源性RB基因的细胞系，与全长pRB蛋白相比，一种约94 kDa的N末端截短的RB蛋白（pRB94）具有更强的细胞生长抑制作用。用表达pRB94的质粒转染的肿瘤细胞表现出多种常与细胞衰老和/或凋亡相关的形态变化。它们无法进入S期并迅速死亡。在受体肿瘤细胞中表达的pRB94半衰期比全长pRB蛋白更长，并且倾向于以活性未磷酸化或低磷酸化形式存在。由于还发现N末端截短的RB蛋白经常在生长停滞和/或分化的肿瘤细胞中积累，我们认为pRB的N末端截短可能是细胞周期调控中调节RB蛋白功能的细胞机制之一。
