This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A major focus of research in the lab is on characterization of potential role of KRAB domain containing zinc finger transcriptional repressors (KRAB-ZNFs) in development of human cancers. Epigenetic silencing of many tumor suppressor genes has emerged recently as a new mechanism of tumor progression. It has been implicated in development of most tumor types and with high frequency. Since KRAB-ZNFs major activity is repression of transcription we pursue a hypothesis that misregulation of KRAB-ZNFs genes may contribute co cancerous phenotype via KRAB-ZNFs mediated repression of tumor suppressor genes or indirect activation of oncogenes. More than 400 members of KRAB-ZNFs family are encoded in the human genome. They all share evolutionary conserved N-terminal KRAB repression domain. We developed several polyclonal antibodies to the conserved A motif in the consensus KRAB domain and performed preliminary analysis of KRAB-ZNF proteins expression in several tissue type-matched normal and cancer cell lines. Both, human breast and lung cancer cell line panels showed differential expression of KRAB-ZNF proteins between primary or immortalized and cancer cells. In search for potential epigenetic silencers we continue our analysis by mass spectrometry identification and characterization of the KRAB-ZNFs differentially expressed in normal versus cancer cells.
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