Maeda Ryu, Ishimura Akihiko, Mood Kathleen, Park Eui Kyun, Buchberg Arthur M, Daar Ira O
Regulation of Cell Growth Laboratory, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD 21702, USA.
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5448-53. doi: 10.1073/pnas.082654899.
Pbx1 is a homeodomain protein that functions in complexes with other homeodomain-containing proteins to regulate gene expression during embryogenesis and oncogenesis. Pbx proteins bind DNA cooperatively as heterodimers or higher order complexes with Meis family members and Hox proteins and are believed to specify cell identity during development. Here, we present evidence that Pbx1, in partnership with Meis1b, can regulate posterior neural markers and neural crest marker genes during Xenopus development. A Xenopus homolog of the Pbx1b homeodomain protein was isolated and shown to be expressed throughout embryogenesis. Xpbx1b expression overlaps with Xmeis1 in several areas, including the lateral neural folds, caudal branchial arch, hindbrain, and optic cup. When ectopically expressed, Xpbx1b can synergize with Xmeis1b to promote posterior neural and neural crest gene expression in ectodermal explants. Further, a physical interaction between these two homeodomain proteins is necessary for induction of these genes in embryonic tissue. In addition, coexpression of Xmeis1b and Xpbx1b leads to a prominent shift in the localization of Xmeis1b from the cytoplasm to the nucleus, suggesting that nuclear transport or retention of Xmeis1b may depend upon Xpbx1b. Finally, expression of a mutant construct in which Xpbx1b protein is fused to the repressor domain from Drosophila Engrailed inhibits posterior neural and neural crest gene expression. These data indicate that Xpbx1b and its partner, Xmeis1b, function in a transcriptional activation complex during hindbrain and neural crest development.
Pbx1是一种同源结构域蛋白，它与其他含同源结构域的蛋白形成复合物，在胚胎发生和肿瘤发生过程中调节基因表达。Pbx蛋白作为异二聚体或与Meis家族成员和Hox蛋白形成更高阶的复合物协同结合DNA，被认为在发育过程中决定细胞身份。在此，我们提供证据表明，在非洲爪蟾发育过程中，Pbx1与Meis1b合作可调节后神经标记物和神经嵴标记基因。分离出了非洲爪蟾Pbx1b同源结构域蛋白的同源物，并显示其在整个胚胎发生过程中均有表达。Xpbx1b的表达在几个区域与Xmeis1重叠，包括外侧神经褶、尾鳃弓、后脑和视杯。异位表达时，Xpbx1b可与Xmeis1b协同作用，促进外胚层外植体中后神经和神经嵴基因的表达。此外，这两种同源结构域蛋白之间的物理相互作用对于胚胎组织中这些基因的诱导是必要的。另外，Xmeis1b和Xpbx1b的共表达导致Xmeis1b的定位从细胞质显著转移到细胞核，这表明Xmeis1b的核转运或滞留可能依赖于Xpbx1b。最后，一种突变构建体的表达，其中Xpbx1b蛋白与果蝇Engrailed的抑制结构域融合，可抑制后神经和神经嵴基因的表达。这些数据表明，Xpbx1b及其伙伴Xmeis1b在hindbrain和神经嵴发育过程中在转录激活复合物中发挥作用。
