Richardson P M, Zon L I
Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts, USA.
Oncogene. 1995 Sep 21;11(6):1139-48.
In an effort to identify genes that are differentially regulated during mast cell development, subtracted cDNA prepared from wild-type murine P815 mastocytoma cells and a P815 subline that exhibits properties of mast cell differentiation was used to screen mast cell cDNA libraries. Several known mast cell-specific cDNAs were isolated including mast cell carboxypeptidase A (MC-CPA), murine mast cell protease-5 (MMCP-5), and gp49. A novel cDNA, designated Tbc1, was identified that showed differential expression in the two mast cell lines. The amino acid sequence predicted from the cDNA contains a 200 amino acid domain that is homologous to regions in the tre-2 oncogene and the yeast regulators of mitosis, BUB2 and cdc16. The N-terminal region contains a number of cysteine and histidine residues, potentially encoding a zinc finger domain. Tbc1 is a nuclear protein and is expressed in highest levels in hematopoietic cells, testis and kidney. Within these tissues, expression of Tbc1 is cell- and stage-specific. Based on sequence similarity, pattern of expression and subcellular localization, Tbc1 may play a role in the cell cycle and differentiation of various tissues.
为了鉴定在肥大细胞发育过程中差异调节的基因，从野生型鼠P815肥大细胞瘤细胞和表现出肥大细胞分化特性的P815亚系制备的扣除cDNA被用于筛选肥大细胞cDNA文库。分离出了几个已知的肥大细胞特异性cDNA，包括肥大细胞羧肽酶A（MC-CPA）、鼠肥大细胞蛋白酶-5（MMCP-5）和gp49。鉴定出一个新的cDNA，命名为Tbc1，它在两种肥大细胞系中表现出差异表达。从该cDNA预测的氨基酸序列包含一个200个氨基酸的结构域，该结构域与tre-2癌基因以及酵母有丝分裂调节因子BUB2和cdc16中的区域同源。N端区域包含许多半胱氨酸和组氨酸残基，可能编码一个锌指结构域。Tbc1是一种核蛋白，在造血细胞、睾丸和肾脏中表达水平最高。在这些组织中，Tbc1的表达具有细胞和阶段特异性。基于序列相似性、表达模式和亚细胞定位，Tbc1可能在各种组织的细胞周期和分化中发挥作用。
