LEF1(淋巴样增强因子1)属于TCF/LEF基因家族,是一个重要的转录因子,主要参与Wnt/β-catenin信号通路的调控。该基因家族(TCF/LEF)的共性是通过结合β-catenin激活下游靶基因的转录,调控细胞增殖、分化和胚胎发育等过程。LEF1在免疫系统(特别是T细胞和B细胞的发育)、毛囊形成、骨骼发育和肠道干细胞维持中发挥关键作用。其表达产物通过与DNA结合并招募共激活因子(如β-catenin)来调节靶基因的表达。LEF1的主要作用位点包括淋巴组织、皮肤和肠道等。突变或异常表达可能导致功能失调,例如LEF1功能丧失性突变与免疫缺陷、毛发生长异常(如少毛症)相关,而过度激活可能与癌症(如结肠癌、白血病)的发生有关。LEF1过表达可能促进细胞增殖和肿瘤发生,尤其在Wnt信号通路异常激活的情况下,会驱动癌基因的表达。相反,LEF1表达降低可能导致免疫细胞发育受阻、毛囊再生障碍或肠道上皮稳态失衡。此外,LEF1与其他基因(如MYC、CCND1)存在相互作用,共同调控细胞周期和分化。在疾病方面,LEF1的异常表达与多种癌症、自身免疫疾病和发育障碍密切相关。例如,在急性淋巴细胞白血病(ALL)中,LEF1的高表达与不良预后相关,而在某些皮肤病中,LEF1功能缺陷可能导致毛囊发育异常。因此,LEF1是一个多功能基因,其精确调控对维持正常生理功能和预防疾病至关重要。
This gene encodes a transcription factor belonging to a family of proteins that share homology with the high mobility group protein-1. The protein encoded by this gene can bind to a functionally important site in the T-cell receptor-alpha enhancer, thereby conferring maximal enhancer activity. This transcription factor is involved in the Wnt signaling pathway, and it may function in hair cell differentiation and follicle morphogenesis. Mutations in this gene have been found in somatic sebaceous tumors. This gene has also been linked to other cancers, including androgen-independent prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
这个基因编码属于一个家族,与高迁移率族蛋白1具有同源性的蛋白质的转录因子。由该基因编码的蛋白质可以结合到在T细胞受体-α增强剂的功能上重要的网站,从而赋予极大增强子活性。此转录因子参与Wnt信号通路,并且它可以在毛细胞分化和毛囊形态的作用。这个基因的突变体中的皮脂腺瘤被发现。这种基因也被链接到其它的癌症,包括雄激素依赖性前列腺癌。选择性剪接结果在多个抄本变形。 [由RefSeq的,2009年10月提供]
LEF1基因(以及对应的蛋白质)的细胞分布位置:
LEF1基因的本体(GO)信息:
名称 |
---|
4310 Wnt signaling pathway [PATH:hsa04310] |
4390 Hippo signaling pathway [PATH:hsa04390] |
4520 Adherens junction [PATH:hsa04520] |
4916 Melanogenesis [PATH:hsa04916] |
5200 Pathways in cancer [PATH:hsa05200] |
5210 Colorectal cancer [PATH:hsa05210] |
5216 Thyroid cancer [PATH:hsa05216] |
5221 Acute myeloid leukemia [PATH:hsa05221] |
5217 Basal cell carcinoma [PATH:hsa05217] |
5215 Prostate cancer [PATH:hsa05215] |
5213 Endometrial cancer [PATH:hsa05213] |
5412 Arrhythmogenic right ventricular cardiomyopathy (ARVC) [PATH:hsa05412] |
名称 |
---|
beta-catenin independent WNT signaling |
binding of TCF/LEF:CTNNB1 to target gene promoters |
Ca2+ pathway |
deactivation of the beta-catenin transactivating complex |
Degradation of beta-catenin by the destruction complex |
formation of the beta-catenin:TCF transactivating complex |
repression of WNT target genes |
Signal Transduction |
Signaling by Wnt |
TCF dependent signaling in response to WNT |
疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
Chronic Lymphocytic Leukemia | 0.241900093 | 8 | 1 | BeFree_CTD_human_GWASCAT |
Colonic Neoplasms | 0.122995792 | 3 | 0 | BeFree_CTD_human_LHGDN |
Sebaceous Gland Neoplasms | 0.12272435 | 1 | 0 | CTD_human_LHGDN |
leukemia | 0.003810118 | 4 | 0 | BeFree_LHGDN |
Mammary Neoplasms | 0.003267234 | 3 | 0 | BeFree_LHGDN |
Colon Carcinoma | 0.003257302 | 12 | 0 | BeFree |
Malignant tumor of colon | 0.003257302 | 12 | 0 | BeFree |
T-Cell Lymphoma | 0.002995792 | 1 | 0 | BeFree_LHGDN |
Peripheral T-Cell Lymphoma | 0.002995792 | 1 | 0 | BeFree_LHGDN |
Neutropenia | 0.002995792 | 2 | 0 | BeFree_LHGDN |
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