Division of Surgical Sciences, Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
Vitam Horm. 2012;88:115-40. doi: 10.1016/B978-0-12-394622-5.00006-7.
Glioma-associated oncogene homolog 1 (GLI1) is the nuclear mediator of Hedgehog signaling that activates gene transcription via its zinc finger DNA-binding and transactivation domains. GLI1 plays a critical role in several cellular processes, including embryonic development, tumorigenesis, and tumor growth and progression. The human GLI1 gene was identified in 1987 as an amplified gene in glioblastoma. Somatic mutations have never been reported in the GLI1 gene in any cell or tumor type. Very recently in 2008-2009, the full-length GLI1 transcript was discovered to undergo alternative splicing to form two shorter isoforms, namely N-terminal deletion variant (GLI1ΔN) and truncated GLI1 (tGLI1). Emerging evidence suggests that the three structurally different GLI1 isoforms are distinctly different in their expression patterns and functions in the context of human cancers. The tGLI1 isoform, in particular, has been shown to gain the ability to modulate expression of the genes that are not regulated by GLI1 and to support the biology of more aggressive cancer. Consequently, a key focus of this chapter is to summarize and compare the properties of the three GLI1 isoforms and their relations to malignant biology of human cancers.
Glioma-associated oncogene homolog 1 (GLI1) 是 Hedgehog 信号的核中介物，通过其锌指 DNA 结合和转录激活结构域激活基因转录。GLI1 在几个细胞过程中发挥关键作用，包括胚胎发育、肿瘤发生以及肿瘤生长和进展。1987 年，人类 GLI1 基因被鉴定为神经胶质瘤中扩增的基因。在任何细胞或肿瘤类型中，从未报道过 GLI1 基因的体细胞突变。直到 2008-2009 年，全长 GLI1 转录本被发现通过选择性剪接形成两种较短的异构体，即 N 端缺失变异体 (GLI1ΔN) 和截断 GLI1 (tGLI1)。新出现的证据表明，三种结构不同的 GLI1 异构体在人类癌症的表达模式和功能方面存在明显差异。特别是 tGLI1 异构体已被证明能够调节不受 GLI1 调节的基因的表达，并支持更具侵袭性的癌症的生物学特性。因此，本章的一个重点是总结和比较三种 GLI1 异构体的特性及其与人类癌症恶性生物学的关系。
