Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ-3/BCL-6 oncogene
Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ-3/BCL-6 oncogene
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DOI：
10.1038/sj.onc.1202332
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发表时间：
1999-01-14
期刊：
影响因子：
8
通讯作者：
Zelent, A
中科院分区：
文献类型：
--
作者：
Davies, JM;Hawe, N;Zelent, A
BTB/POZ结构域C2 H2锌指蛋白是由果蝇间隙基因kruppel相关的一个基因亚家族编码的。到目前为止，两种这样的蛋白质，PLZF和LAZ-3/BCL-6，已经涉及肿瘤发生。我们现在已经鉴定了该gent亚家族的一个新成员，其编码62 kDa的锌指蛋白，称为LRF，具有与PLZF高度相似的BTB/POZ结构域。人和小鼠LRF基因均定位于同线染色体区域（分别为19p13.3和10B5.3），在成人组织和细胞系中广泛表达。在胚胎发育约9.5-10.0天，小鼠LRF基因在肢芽、咽弓、尾芽、胎盘和神经管中表达。LRF蛋白在体内与LAZ-3/BCL-6相关，但不与PLZF相关。尽管LRF或LAZ-3/BCL-6、BTB/POZ结构域可以容易地同二聚化，但在体内LRF和LAZ-3/BCL-6 BTB/POZ结构域之间没有检测到异二聚化，并且全长LRF和LAZ-3/BCL-6之间的相互作用需要每个伴侣蛋白中存在BTB/POZ结构域和锌指。正如从上述结果所预期的，LRF和LAZ-3/BCL-6也在核中彼此共定位。两者合计，我们的研究结果表明，BTB/POZ结构域锌指蛋白可能作为同源和异源二聚体复合物的形成，因此，其下游靶基因的转录所产生的影响，是由一个给定的伴侣蛋白的水平和表达结构域。
BTB/POZ-domain C2H2 zinc(Zn)-finger proteins are encoded by a subfamily of genes related to the Drosophila gap gene kruppel. To date, two such proteins, PLZF and LAZ-3/BCL-6, have been implicated in oncogenesis. We have now identified a new member of this gent subfamily which encodes a 62 kDa Zn-finger protein, termed LRF, with a BTB/POZ domain highly similar to that of PLZF, Both human and mouse LRF genes, which localized to syntenic chromosomal regions (19p13.3 and 10B5.3, respectively), were widely expressed in adult tissues and cell lines. At approximately 9.5-10.0 days of embryonic development, the mouse LRF gene was expressed in the limb buds, pharyngeal arches, tail bud, placenta and neural tube. The LRF protein associated in vivo with LAZ-3/BCL-6, but not with PLZF to which it was more related. Although the LRF, or LAZ-3/BCL-6, BTB/POZ domain could readily homodimerize, no heterodimerization was detected in vivo between the LRF and LAZ-3/BCL-6 BTB/POZ domains and interaction between full length LRF and LAZ-3/BCL-6 required the presence of both the BTB/POZ domain and Zn-fingers in each partner protein. As expected from the above results, LRF and LAZ-3/BCL-6 also colocalized with each other in the nucleus. Taken together, our findings suggest that BTB/POZ-domain Zn-finger proteins may function as homo and heterodimeric complexes whose formation, and hence the resultant effect on transcription of their downstream target genes, is determined by the levels and expression domains of a given partner protein.