Disease relevance of ZNF43

• Expression and regulation of the transcriptional repressor ZNF43 in Ewing sarcoma cells [1].
• We propose that aurora2 may be a target of this amplicon since its DNA is amplified and its RNA overexpressed, in more than 50% of primary colorectal cancers [2].
• This HCC marker set contained several cancer-related genes, including serine/threonine kinase 15 (STK15), which has been implicated in chromosome segregation abnormalities but which has not been linked previously with liver cancer [3].
• The aneuploid seminomas and nonseminomas tumors (including CIS) showed increased numbers of centrosomes, without STK15 amplification or overexpression [4].
• The clinical significance of Aurora-A/STK15/BTAK expression in human esophageal squamous cell carcinoma [5].

High impact information on ZNF43

• Here we demonstrate that the aurora2 gene maps to chromosome 20q13, a region amplified in a variety of human cancers, including a significant number of colorectal malignancies [2].
• We have identified two human homologues of these genes, termed aurora1 and aurora2, that encode cell-cycle-regulated serine/threonine kinases [2].
• Furthermore, overexpression of aurora2 transforms rodent fibroblasts [2].
• These observations implicate aurora2 as a potential oncogene in many colon, breast and other solid tumors, and identify centrosome-associated proteins as novel targets for cancer therapy [2].
• Alterations in the expression and activity of the centrosomal kinase, Aurora-A/serine/threonine kinase 15 (STK15), affect genomic stability, disrupt the fidelity of centrosome duplication, and induce cellular transformation [6].

Chemical compound and disease context of ZNF43

• Polymorphisms of the AURKA (STK15/Aurora Kinase) Gene and Breast Cancer Risk (United States) [7].

Biological context of ZNF43

• The predicted protein structure of this cDNA (ZNF43) showed that it contained 22 of the Krüppel type of zinc finger motifs in tandem [8].
• Aneuploidy has been associated with centrosome aberrations, sometimes related to overexpression of STK15 [4].
• We investigated aneuploidy, centrosome aberrations and the role of STK15 in different types of testicular germ cell tumors as well as in normal and disturbed spermatogenesis [4].
• Here we demonstrate that the Aurora2 protein is degraded rapidly after G2/M phase release in mammalian cells [9].
• Compared with normal epithelium, significant up-regulation of mRNAs was already present for Aurora-A/STK15 (p = 0.0313) in dysplastic cells and for all investigated markers in invasive carcinoma [10].

Anatomical context of ZNF43

• The expression of the ZNF43 gene was mainly limited to T and B cell lines [8].
• After in vitro induced terminal differentiation of the human HL60 cell line the expression of the ZNF43 family was reduced [8].
• Therefore, aneuploidy of testicular germ cell tumors is associated with amplified centrosomes probably unrelated to STK15 [4].
• Germ cells in seminiferous tubules with disturbed spermatogenesis shared both aneuploidy and centrosome abnormalities with seminomas/nonseminomas and showed a more intense STK15 staining than those with normal spermatogenesis and CIS [4].
• Using immunofluorescence staining, Northern and Western blot analyses, we verified that overexpression of Aurora-A/STK15 in bladder tumor cell lines enhanced chromosomal instability [11].

Associations of ZNF43 with chemical compounds

• ARK-1, a cytoplasmic tyrosine kinase, appears to be a negative regulator of multiple pathways in C. elegans [12].

Analytical, diagnostic and therapeutic context of ZNF43

• Southern blotting showed that ZNF43 was one of a closely related family of proteins with 10 to 20 members [8].
• Southern blotting confirmed the amplification frequency of the STK15 gene, which had been previously detected by comparative PCR [13].

References