干旱区生态环境知识资源中心(Arid): RIPK3 activation induces TRIM28 derepression in cancer cells and enhances the anti-tumor microenvironment

Arid

DOI	10.1186/s12943-021-01399-3
	RIPK3 activation induces TRIM28 derepression in cancer cells and enhances the anti-tumor microenvironment
	Park, Han-Hee; Kim, Hwa-Ryeon; Park, Sang-Yeong; Hwang, Sung-Min; Hong, Sun Mi; Park, Sangwook; Kang, Ho Chul; Morgan, Michael J.; Cha, Jong-Ho; Lee, Dakeun; Roe, Jae-Seok; Kim, You-Sun
通讯作者	Kim, YS (corresponding author), Ajou Univ, Sch Med, Dept Biochem, Suwon 16499, South Korea. ; Kim, YS (corresponding author), Ajou Univ, Grad Sch, Dept Biomed Sci, Suwon 16499, South Korea. ; Roe, JS (corresponding author), Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biochem, Seoul 03722, South Korea.
来源期刊	MOLECULAR CANCER
EISSN	1476-4598
出版年	2021
卷号	20 期号:1
英文摘要	Background: Necroptosis is emerging as a new target for cancer immunotherapy as it is now recognized as a form of cell death that increases tumor immunogenicity, which would be especially helpful in treating immune-desert tumors. De novo synthesis of inflammatory proteins during necroptosis appears especially important in facilitating increased anti-tumor immune responses. While late-stage transcription mediated by NF-kappa B during cell death is believed to play a role in this process, it is otherwise unclear what cell signaling events initiate this transactivation of inflammatory genes. Methods: We employed tandem-affinity purification linked to mass spectrometry (TAP-MS), in combination with the analysis of RNA-sequencing (RNA-Seq) datasets to identify the Tripartite Motif Protein 28 (TRIM28) as a candidate co-repressor. Comprehensive biochemical and molecular biology techniques were used to characterize the role of TRIM28 in RIPK3 activation-induced transcriptional and immunomodulatory events. The cell composition estimation module was used to evaluate the correlation between RIPK3/TRIM28 levels and CD8(+) T cells or dendritic cells (DC) in all TCGA tumors. Results: We identified TRIM28 as a co-repressor that regulates transcriptional activity during necroptosis. Activated RIPK3 phosphorylates TRIM28 on serine 473, inhibiting its chromatin binding activity, thereby contributing to the transactivation of NF-kappa B and other transcription factors, such as SOX9. This leads to elevated cytokine expression, which then potentiates immunoregulatory processes, such as DC maturation. The expression of RIPK3 has a significant positive association with the tumor-infiltrating immune cells populations in various tumor type, thereby activating anti-cancer responses. Conclusion: Our data suggest that RIPK3 activation-dependent derepression of TRIM28 in cancer cells leads to increased immunostimulatory cytokine production in the tumor microenvironment, which then contributes to robust cytotoxic anti-tumor immunity.
英文关键词	RIPK3 TRIM28 NF-kappa B Transcriptional regulator Chromatin Immunostimulatory cytokines
类型	Article
语种	英语
开放获取类型	gold, Green Published
收录类别	SCI-E
WOS记录号	WOS:000687167700002
WOS关键词	EXPRESSION ; PHOSPHORYLATION ; PROMOTES ; STAT3 ; PROTEINS ; NECROSIS ; GENES ; ROLES ; DEATH ; MLKL
WOS类目	Biochemistry & Molecular Biology ; Oncology
WOS研究方向	Biochemistry & Molecular Biology ; Oncology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/364187
作者单位	[Park, Han-Hee; Park, Sang-Yeong; Hwang, Sung-Min; Hong, Sun Mi; Kim, You-Sun] Ajou Univ, Sch Med, Dept Biochem, Suwon 16499, South Korea; [Park, Han-Hee; Park, Sang-Yeong; Park, Sangwook; Kang, Ho Chul; Kim, You-Sun] Ajou Univ, Grad Sch, Dept Biomed Sci, Suwon 16499, South Korea; [Kim, Hwa-Ryeon; Roe, Jae-Seok] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biochem, Seoul 03722, South Korea; [Park, Sangwook; Kang, Ho Chul] Ajou Univ, Sch Med, Dept Physiol, Suwon 16499, South Korea; [Morgan, Michael J.] Northeastern State Univ, Dept Nat Sci, Tahlequah, OK 74464 USA; [Cha, Jong-Ho] Inha Univ, Coll Med, Dept Biomed Sci, Incheon 22212, South Korea; [Cha, Jong-Ho] Inha Univ, Grad Sch, Dept Biomed Sci & Engn, Incheon 22212, South Korea; [Lee, Dakeun] Ajou Univ, Sch Med, Dept Pathol, Suwon 16499, South Korea
推荐引用方式 GB/T 7714	Park, Han-Hee,Kim, Hwa-Ryeon,Park, Sang-Yeong,et al. RIPK3 activation induces TRIM28 derepression in cancer cells and enhances the anti-tumor microenvironment[J],2021,20(1).
APA	Park, Han-Hee.,Kim, Hwa-Ryeon.,Park, Sang-Yeong.,Hwang, Sung-Min.,Hong, Sun Mi.,...&Kim, You-Sun.(2021).RIPK3 activation induces TRIM28 derepression in cancer cells and enhances the anti-tumor microenvironment.MOLECULAR CANCER,20(1).
MLA	Park, Han-Hee,et al."RIPK3 activation induces TRIM28 derepression in cancer cells and enhances the anti-tumor microenvironment".MOLECULAR CANCER 20.1(2021).