Disruption of Sept6, a fusion partner gene of MLL, does not affect ontogeny, leukemogenesis induced by MLL-SEPT6, or phenotype induced by the loss of Sept4
Disruption of Sept6, a fusion partner gene of MLL, does not affect ontogeny, leukemogenesis induced by MLL-SEPT6, or phenotype induced by the loss of Sept4
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DOI：
10.1128/mcb.25.24.10965-10978.2005
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发表时间：
2005-12-01
影响因子：
5.3
通讯作者：
Nosaka, T
中科院分区：
文献类型：
--
作者：
Ono, R;Ihara, M;Nosaka, T
Septin 是进化上保守的 GTP 结合蛋白，可以异聚成丝。最近的研究表明，脓毒症不仅参与多种正常细胞过程，还参与多种疾病（包括癌症）的发病机制。 SEPT6 在组织中广泛表达，是急性白血病 11q23 易位中 MLL 的融合伴侣基因之一。然而，这种脓毒症在体内的作用仍然难以捉摸。我们培育出了 Sept6 缺陷小鼠，它们既没有表现出明显的异常、胞质分裂的变化，也没有表现出自发性恶性肿瘤。 Sept6缺陷不会导致本研究中评估的任何脓毒症发生任何数量变化，也不会导致Sept4缺陷小鼠发生任何额外的变化。即使是 Sept11（Sept6 的密切同源物）的耗尽，在体外也不影响 Sept6-null 细胞，因此意味着 septin 系统中存在高度冗余。此外，Sept6的缺失并没有改变MLL-SEPT6诱导的骨髓增殖性疾病的表型，因此表明Sept6不具有肿瘤抑制因子的功能。据我们所知，这是第一份证明 11q23 易位中 MLL 易位伴侣基因的破坏不会导致 MLL 融合基因导致白血病发生的第一份报告。
Septins are evolutionarily conserved GTP-binding proteins that can heteropolymerize into filaments. Recent studies have revealed that septins are involved in not only diverse normal cellular processes but also the pathogenesis of various diseases, including cancer. SEPT6 is ubiquitously expressed in tissues and one of the fusion partner genes of MLL in the 11q23 translocations implicated in acute leukemia. However, the roles of this septin in vivo remain elusive. We have developed Sept6-deficient mice that exhibited neither gross abnormalities, changes in cytokinesis, nor spontaneous malignancy. Sept6 deficiency did not cause any quantitative changes in any of the septins evaluated in this study, nor did it cause any additional changes in the Sept4-deficient mice. Even the depletion of Sept11, a close homolog of Sept6, did not affect the Sept6-null cells in vitro, thus implying a high degree of redundancy in the septin system. Furthermore, a loss of Sept6 did not alter the phenotype of myeloproliferative disease induced by MLL-SEPT6, thus suggesting that Sept6 does not function as a tumor suppressor. To our knowledge, this is the first report demonstrating that a disruption of the translocation partner gene of MLL in 11q23 translocation does not contribute to leukemogenesis by the MLL fusion gene.