375회 Role of RIZ1 Tumor Suppressor as a Histone Methyltransferase and …

375회

연사 :  김 근 철, 강원대학교 생물학과 분자생물학실험실

제목:  Role of RIZ1 Tumor Suppressor as a Histone Methyltransferase and a Transcriptional Regulator in Human Cancers

Abstract

  RIZ1 is identified as a RB-Interacting zinc finger protein using the functional screening technique. Genetic studies and molecular studies have suggested that RIZ1 acts as one of tumor suppressor in human cancers. Recently, our group has started the RIZ1 functional studies with several functional domains in RIZ1.

PR domain has high homology with SET domain, which has the HMTase enzyme activity and implicates in chromosome regulation. To address if RIZ1 has HMTase activity, we performed HMT assay with Ad-RIZ1 infected cells, Histone peptide, GST-histone, and protein fraction. And then we show PR domain in RIZ1 has HMTase activity toward Histone H3. RIZ1 methylation reaction can be regulated by SAM/SAH level in the cells. With these results, we make an important hypothesis which RIZ1 HMTase activity might be correlatedwith dietary carcinogenesis in sporadic cancer.

LxxLL motif is implicated in nuclear hormone signaling and transcriptional regulation in terms of cooperation with other proteins. To expand our knowledge that LxxLL motif in RIZ1 is mediating the estrogen signaling, we performed a promoter assay, and a binding assay. RIZ1 interacted with SRC1 and p300, suggesting that the coactivator function of RIZ1 may be mediated by its interaction with other transcriptional coactivators. Estrogen treatment modulates RIZ1 HMTase activity and target promoter binding activity. Introduction of RIZ1 SiRNA correlated with decreased induction of pS2 gene by estrogen in MCF7 cells. With these data, we suggest that a histone methyltransferase is required for optimal estrogen response.