ZNF418, a novel human KRAB/C2H2 zinc finger protein, suppresses MAPK signaling pathway

Abstract

Cardiac differentiation involves a cascade of coordinated gene expression that regulates cell proliferation and matrix protein formation in a defined temporal-spatial manner. Zinc finger-containing transcription factors have been implicated as critical regulators of multiple cardiac-expressed genes, and are thought to be important for human heart development and diseases. Here, we have identified and characterized a novel zinc finger gene named ZNF418 from a human embryo heart cDNA library. The gene spans 13.5 kb on chromosome 19q13.43 encompassing six exons, and transcribes a 3.7-kb mRNA that encodes a protein with 676 amino acid residues. The predicted protein contains a KRAB-A box and 17 tandem C2H2 type zinc finger motifs. Northern blot analysis indicates that ZNF418 is expressed in multiple fetal and adult tissues, but is expressed at higher levels in the heart. Reporter gene assays show that ZNF418 is a transcriptional repressor, and the KRAB motif of ZNF418 represents the basal repressive domain. Overexpression of ZNF418 in COS-7 cells inhibits the transcriptional activity of SRE and AP-1 which may be silenced by siRNA. These results suggest that ZNF418 is a member of the zincfinger transcription factor family and may act as a negative regulator in MAPK signaling pathway.

Tumor suppressor BLU inhibits proliferation of nasopharyngeal carcinoma cells by regulation of cell cycle, c-Jun N-terminal kinase and the cyclin D1 promoter

“…They are serine/threonine protein kinases that can be activated by a variety of stimuli including environmental stress (UV and ionizing radiation, heat shock, osmotic or redox shock), inflammatory cytokines, and growth factors. Different species of zinc finger proteins function to regulate gene transcription, similar with ZNF418 [24], a member of the zinc finger transcription factor family. BLU may negatively regulate gene transcription mediated by the MAPK signaling pathways through transcriptionally regulating a molecule(s) yet to be identified.…”

A novel human KRAB-related zinc finger gene ZNF425 inhibits mitogen-activated protein kinase signaling pathway

“…Although more than one hundred members of the KRAB/C2H2 zinc-finger protein family have been described, little is known of their biological function (12). Increasingly, studies have implicated ZNF proteins in embryonic development and disease (1,(13)(14)(15)(16)(17)(18). For example, the Kruppel-class C2H2 zinc-finger protein ZNF382 has been shown to play a role in myogenesis (13, Wu, unpublished) and in tumor suppression through heterochromatin-mediated silencing (17).…”

“…The multitype U-shaped functions of zinc-finger proteins in heart cells of Drosophila embryo have been reported (7). Some ZNF proteins, such as ZNF480 (14), ZNF569 (15) and ZNF418 (16), have been shown to be involved in cellular functions via the MAPK signaling pathway.…”

Proteomic analysis of human oral verrucous carcinoma

“…Other roles include regulation of genes involved in the stress response as well as pleiotropic drug resistance, as demonstrated in budding yeast and in human fungal pathogens. With the number of characterized zinc cluster proteins growing rapidly, it is becoming more and more important (Li et al, 2008;Li et al, 2007;Huang et al, 2007). The putative adaptor protein D53, a member of the D52-like family, works as a novel 14-3-3 binding partner in breast cancer cells9 (Boutros et al, 2003).…”