This entry represents the zinc finger CCCH-type with G patch domain-containing protein (ZIP) that acts as a transcription repressor through the recruitment of the Mi-2/nucleosome remodelling and deacetylase (NuRD) complex to target promoters. ZIP regulates several cellular signalling pathways like the epidermal growth factor receptor (EGFR) pathways, critically involved in cell proliferation, survival, and migration.ZIP contains several domains: a CCCH zinc finger, a TUDOR domain, a G-patch and a coiled-coil domain. The coiled-coil domain is responsible for the ZIP interaction with Mi-2 to recruit the NuRD complex, while its zinc finger structure specifically recognises the consensus sequence in the 5' upstream region of EGFR. The TUDOR domain is a chromatin-presenting module reading the methylated histone marks. ZIP is also involved in the recognition of RNA and other proteins, suggesting that it may coordinate an active coupling between transcription regulation and pre-mRNA splicing, especially considering that ZIP contains a CCCH-type of zinc finger and a G-patch domain, both of which have been featured in proteins functioning in mRNA processing. Additionally, ZIP inhibits cell proliferation and suppresses breast carcinogenesis, while its depletion leads to a drastic tumour growth in vivo. ZIP is downregulated in breast carcinomas and that its level of expression is negatively correlated with that of EGFR [].
