ZNF424, a novel human KRAB/C2H2 zinc finger protein, suppresses NFAT and p21 pathway.
Zinc finger-containing transcription factors are the largest single family of transcriptional regulators in mammals, which play an essential role in cell differentiation, cell proliferation, apoptosis, and neoplastic transformation. Here we have cloned a novel KRAB-related zinc finger gene, ZNF424, encoding a protein of 555aa. ZNF424 gene consisted of 4 exons and 3 introns, and mapped to chromosome 19p13.3. ZNF424 gene was ubiquitously expressed in human embryo tissues by Northern blot analysis. ZNF424 is conserved across species in evolution. Using a GFP-labeled ZNF424 protein, we demonstrate that ZNF424 localizes mostly in the nucleus. Transcriptional activity assays shows ZNF424 suppresses transcriptional activity of L8G5-luciferase. Overexpression of ZNF424 in HEK- 293 cells inhibited the transcriptional activity of NFAT and p21, which may be silenced by siRNA. The results suggest that ZNF424 protein may act as a transcriptional repressor that suppresses NFAT and p21 pathway to mediate cellular functions.
Wang
Yuequn
Y
The Center for Heart Development, College of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, P. R. of China.
Zhou
Junmei
J
Ye
Xiangli
X
Wan
Yongqi
Y
Li
Yongqing
Y
Mo
Xiaoyan
X
Yuan
Wuzhou
W
Yan
Yan
Y
Luo
Na
N
Wang
Zequn
Z
Fan
Xiongwei
X
Deng
Yun
Y
Wu
Xiushan
X
D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D050778:NFATC Transcription Factors / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D016335:Zinc Fingers
D050759:Cyclin-Dependent Kinase Inhibitor p21; D050778:NFATC Transcription Factors; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C550626:ZNF57 protein, human