What is Krueppel C2H2-Type Zinc-Finger Protein Family?

Krueppel C2H2-Type Zinc-Finger Protein Family, one of the C2H2-type ZNFs that is conserved throughout evolution, is involved in preserved biological activities, such as general transcriptional regulation and development/differentiation of organs/tissues observed in the early embryonic phase.

Krueppel C2H2-Type Zinc-Finger Protein Family is divided into 2 main classes including ZFX and ZFY.

 --ZFX

The Zinc finger X-chromosomal protein (ZFX), a novel member of the Krueppel C2H2-type zinc-finger protein family, has been implicated in multiple human cancers. ZFX is highly expressed in malignant tumors, such as laryngeal squamous cell carcinoma, hepatocellular carcinoma, gastric carcinoma and colorectal cancer, suggesting that this protein may have important functions in the malignant transformation of these cell types, and is also involved various physiological functions such as proliferation, differentiation, cell cycle and cell death. There is a potential that ZFX will be a target for cancer diagnosis as well as drug therapy.

Gallbladder carcinoma (GBC) is one of the most aggressive and fatal malignancies. Zinc finger X-chromosomal protein (ZFX) was a novel member of the Krueppel C2H2-type zinc-finger protein family and its down-regulation led to impaired cell growth in human laryngeal squamous cell carcinoma. Loss of function analysis was performed on GBC cell line (GBC-SD) using lentivirus-mediated siRNA against ZFX. The proliferation, in vitro tumorigenesis (colony-formation) ability as well as cell migration was significantly suppressed after GBC-SD cells were infected with ZFX-siRNA-expressing lentivirus (Lv-shZFX), suggesting that ZFX promoted the growth and migration of GBC cells and could present a potential molecular target for gene therapy of GBC. Ongoing studies about the molecular mechanism responsible for the regulation role of ZFX will extend our understanding of tumorigenesis in GBC.

 --ZFY

Like in humans, both bovine ZFY and ZFX contain 13 zinc finger motifs and belong to Krueppel C2H2-Type Zinc-Finger Protein Family. All vertebrate ZFX and ZFY proteins comprise a two-domain structure. Encoded by exon 11, a carboxy-terminal half harbors a stretch of 13 C(2)H(2) zinc fingers. Within ZFX or ZFY proteins, a conserved polyalanine motif has been identified. The evolutionary studies on sex chromosomes contribute to understanding the function and structure of the mammalian ZFX and ZFY genes. Knowledge of the ZFX and ZFY exon-intron organization will have practical applications, such as facilitating the sexing of early bovine and porcine embryos.

The zinc-finger domain is a new focal point for understanding Krueppel C2H2-Type Zinc-Finger Protein Family's normal and tumorigenic functions, and for development of molecularly-targeted therapeutics.