Transglutaminase 2 mediates transcriptional regulation through BAF250a polyamination

Hyo-Jun Kim; Jin-Haeng Lee; Sung-Yup Cho; Ju-Hong Jeon; In-Gyu Kim

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자료유형: 학술저널

저자정보: Hyo-Jun Kim (Seoul National University College of Medicine) Jin-Haeng Lee (Seoul National University College of Medicine) Sung-Yup Cho (Seoul National University College of Medicine) Ju-Hong Jeon (Seoul National University College of Medicine) In-Gyu Kim (Seoul National University College of Medicine)

저널정보: 한국유전학회 Genes & Genomics Genes & Genomics Vol.43 No.4

발행연도: 2021.1

수록면: 333 - 342 (10page)

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Background Transglutaminase 2 (TG2) mediates protein modifications by crosslinking or by incorporating polyamine in response to oxidative or DNA-damaging stress, thereby regulating apoptosis, extracellular matrix formation, and inflammation. The regulation of transcriptional activity by TG2-mediated histone serotonylation or by Sp1 crosslinking may also contribute to cellular stress responses. Objective In this study, we attempted to identify TG2-interacting proteins to better understand the role of TG2 in transcriptional regulation. Methods Using a yeast two-hybrid assay to screen a HeLa cell cDNA library, we found that TG2 bound BAF250a, a core subunit of the cBAF chromatin remodeling complex, through an interaction between the TG2 barrel 1 and BAF250a C-terminal domains. Results TG2 was pulled down with a GST-BAF250a C-term fusion protein. Moreover, TG2 and BAF250a were co-fractionated using P11 chromatography, and co-immunoprecipitated. A transamidation reaction showed that TG2 mediated incorporation of polyamine into BAF250a. In glucocorticoid response-element reporter-expressing cells, TG2 overexpression increased the luciferase reporter activity in a transamidation-dependent manner. In addition, a comparison of genome-wide gene expression between wild-type and TG2-deficient primary hepatocytes in response to dexamethasone treatment showed that TG2 further enhanced or suppressed the expression of dexamethasone-regulated genes that were identified by a gene ontology enrichment analysis. Conclusion Thus, our results indicate that TG2 regulates transcriptional activity through BAF250a polyamination.

#Transglutaminase 2 (TG2) · BAF250a · Transamidation · Dexamethasone · Transcriptional activity

참고문헌 (37)

참고문헌 신청

Daniel Aeschlimann / 1998 / Isolation of a cDNA Encoding a Novel Member of the Transglutaminase Gene Family from Human Keratinocytes / Journal of Biological Chemistry 273(6):3452~3460

Lingbao Ai / 2008 / The transglutaminase 2 gene ( TGM2 ), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer / Carcinogenesis 29(3):510~518

Sung-Yup Cho / 2020 / Transglutaminase 2 mediates hypoxia-induced selective mRNA translation via polyamination of 4EBPs / Life Science Alliance 3(3):e201900565

Kihang Choi / 2005 / Chemistry and Biology of Dihydroisoxazole Derivatives: Selective Inhibitors of Human Transglutaminase 2 / Chemistry & Biology 12(4):469~475

Vincenzo De Laurenzi / 2001 / Gene Disruption of Tissue Transglutaminase / Molecular and Cellular Biology 21(1):148~155

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