Functional analyses of the new tumor suppressor candidate gene in hematological malignancies

B淋巴细胞诱导成熟蛋白-1 （Blimp-1）是一种转录抑制因子，据报道是许多细胞系分化所必需的。我们之前发现，Blimp-1位于淋巴细胞恶性肿瘤中纯合缺失的共同区域内，并在原发性淋巴细胞肿瘤中发生突变，这表明Blimp-1具有肿瘤抑制作用。本文主要研究Blimp-1对细胞周期调控的影响。外源表达Blimp-1可快速诱导p53、p57和p21的表达，细胞停留在G1/G0和G2/M期。进一步研究表明，Blimp-1诱导的G1/G0阻滞依赖于野生型pRb，而其对G2/M阻滞的作用需要p53的功能，并且作为pRb的上游调控因子，Blimp-1诱发的p57和p21在保持pRb活性方面发挥协同作用。在恶性淋巴瘤中检测到的Blimp-1突变也被发现在细胞周期阻滞中失去功能。这些结果表明，Blimp-1在细胞周期控制中起重要作用，从而抑制肿瘤的形成。

B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional repressor and is reported to be required for differentiation of many cell lineages. We have previously found that Blimp-1 is located within a common region homozygously deleted in lymphoid malignancies and is mutated in primary lymphoid tumors, suggesting that Blimp-1 has a tumor suppressor role. Here we focus on investigating the effect of Blimp-1 on cell cycle regulation. Exogenous expression of Blimp-1 rapidly induces the expression of p53, p57 and p21, and the cells are arrested at G1/G0 and G2/M phases. Further investigations showed that Blimp-1 induced G1/G0 arrest is dependent on wild type pRb while its effect on G2/M arrest requires functional p53, and as the upstream regulators of pRb, p57 and p21 evoked by Blimp-1 play the cooperative roles on keeping active pRb. A Blimp-1 mutation detected in malignant lymphoma was also found to lose its function in cell cycle arrest. These results suggest that Blimp-1 plays an important role in cell cycle control and therefore the suppression of tumor formation.