ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription
ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription
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DOI：
10.1016/j.molimm.2006.02.029
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发表时间：
2007-01-01
影响因子：
3.6
通讯作者：
Fontes, Joseph D.
中科院分区：
文献类型：
--
作者：
Al-Kandari, Wafa;Jambunathan, Srikarthika;Fontes, Joseph D.
II类反式激活因子（CIITA）被认为是主要组织相容性复合体（MHC）II类基因转录的主要调节因子，并有助于MHC I类基因的转录。为了更好地了解CIITA的功能，我们将CIITA的C端807个氨基酸进行酵母双杂交，克隆了一个新的人类锌指，X连锁重复家族成员C（Zinc finger，X-linked，duplicated family member C，ZXDC）。ZXDC蛋白由858个氨基酸组成，含有10个锌指和一个转录激活结构域，并与CIITA中富含亮氨酸的重复序列相互作用。ZXDC在人细胞系中的过表达导致CIITA对MHC I类和II类启动子的超活化。相反，ZXDC表达的沉默降低了CIITA激活MHC II类基因转录的能力。鉴于ZXDC和CIITA蛋白之间的特异性相互作用，以及ZXDC对MHC基因转录的影响，ZXDC似乎是MHC I类和II类转录的重要调节因子。(c)2006爱思唯尔有限公司保留所有权利。
The class II trans-activator (CIITA) is recognized as the master regulator of major histocompatibility complex (MHC) class II gene transcription and contributes to the transcription of MHC class I genes. To better understand the function of CIITA, we per-formed yeast two-hybrid with the C-terminal 807 amino acids of CIITA, and cloned a novel human cDNA named zinc finger, X-linked, duplicated family member C (ZXDC). The 858 amino acid ZXDC protein contains 10 zinc fingers and a transcriptional activation domain, and was found to interact with the region of CIITA containing leucine-rich repeats. Over-expression of ZXDC in human cell lines resulted in super- activation of MHC class I and class II promoters by CIITA. Conversely, silencing of ZXDC expression reduced the ability of CIITA to activate transcription of MHC class II genes. Given the specific interaction between the ZXDC and CIITA proteins, as well as the effect of ZXDC on MHC gene transcription, it appears that ZXDC is an important regulator of both MHC class I and class II transcription. (c) 2006 Elsevier Ltd. All ri-hts reserved.