TRIM65 determines the fate of a novel subtype of pituitary neuroendocrine tumors via ubiquitination and degradation of TPIT

doi:10.1093/neuonc/noac053

科研成果详情

题名	TRIM65 determines the fate of a novel subtype of pituitary neuroendocrine tumors via ubiquitination and degradation of TPIT
作者	Yao, Hong 1; Xie, Wanqun 1; Dai, Yuting 2; Liu, Yanting 1; Gu, Weiting 1; Li, Jianfeng 2; Wu, Liang 2; Xie, Jing 3; Rui, Weiwei 3; Ren, Bohan 4; Xue, Li 1; Cheng, Yijun 1; Lin, Shaojian 1; Li, Changsheng 1; Tang, Hao 1; Wang, Yu 4; Lou, Meiqing 5; Zhang, Xiaobiao 6; Hu, Ronggui 7; Shang, Hanbing 1; Huang, Jinyan 2; Wu, Zhe Bao 1,4
发表日期	2022-08-01
发表期刊	Neuro-oncology 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Cushing's disease PitNETs TPIT TRIM65 ubiquitination.
其他关键词	UBIQUITYLATION ; TRANSCRIPTION
摘要	Background:Pituitary neuroendocrine tumors (PitNETs) are common intracranial tumors that are classified into seven histological subtypes, including lactotroph, somatotroph, corticotroph, thyrotroph, gonadotroph, null cell, and plurihormonal PitNETs. However, the molecular characteristics of these types of PitNETs are not completely clear. Methods:A total of 180 consecutive cases of PitNETs were collected to perform RNA sequencing. All subtypes of PitNETs were distinguished by unsupervised clustering analysis. We investigated the regulation of TPIT by TRIM65 and its effects on ACTH production and secretion in ACTH-secreting pituitary cell lines, as well as in murine models using biochemical analyses, confocal microscopy, and luciferase reporter assays. Results:A novel subtype of PitNETs derived from TPIT lineage cells was identified as with normal TPIT transcription but with lowered protein expression. Furthermore, for the first time, TRIM65 was identified as the E3 ubiquitin ligase of TPIT. Depending on the RING domain, TRIM65 ubiquitinated and degraded the TPIT protein at multiple Lys sites. In addition, TRIM65-mediated ubiquitination of TPIT inhibited POMC transcription and ACTH production to determine the fate of the novel subtype of PitNETs in vitro and in vivo. Conclusion:Our studies provided a novel classification of PitNETs and revealed that the TRIM65-TPIT complex controlled the fate of the novel subtype of PitNETs, which provides a potential therapy target for Cushing's disease.
资助项目	National Natural Science Foundation of China [82141114, 81972339, 82000749]; National Research Center for Translational Medicine [NRCTM (SH)2019-05]; Shanghai Municipal Science and Technology Commission [18XD1403400]; Qiusuo Funds for Distinguished Young Scholars
出版者	OXFORD UNIV PRESS INC
出版地	CARY
ISSN	1522-8517
EISSN	1523-5866
卷号	24 期号:8 页码:1286-1297
DOI	10.1093/neuonc/noac053
页数	12
WOS类目	Oncology ; Clinical Neurology
WOS研究方向	Oncology ; Neurosciences & Neurology
WOS记录号	WOS:000784521300001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
Pubmed记录号	35218667
Scopus记录号	2-s2.0-85135499961
自科自定义期刊分类	T3(B)类
通讯作者地址	[Wu, Zhe Bao]Department of Neurosurgery,Center of Pituitary Tumor,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200025,China
scopus学科分类	Oncology;Neurology (clinical);Cancer Research
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/33643
专题	附属第一医院_神经外科
通讯作者	Wu, Zhe Bao
作者单位	1.Department of Neurosurgery,Center of Pituitary Tumor,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200025,China; 2.Shanghai Institute of Hematology,State Key Laboratory of Medical Genomics,National Research Center for Translational Medicine,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China; 3.Department of Pathology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China; 4.Department of Neurosurgery,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 5.Department of Neurosurgery,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China; 6.Department of Neurosurgery,Zhongshan Hospital,Fudan University,Shanghai,China; 7.State Key Laboratory of Systems Biology,Cas Center for Excellence in Molecular Cell Science,Innovation Center for Cell Signaling Network,Shanghai Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai,China
推荐引用方式 GB/T 7714	Yao, Hong,Xie, Wanqun,Dai, Yuting,et al. TRIM65 determines the fate of a novel subtype of pituitary neuroendocrine tumors via ubiquitination and degradation of TPIT[J]. Neuro-oncology,2022,24(8):1286-1297.
APA	Yao, Hong., Xie, Wanqun., Dai, Yuting., Liu, Yanting., Gu, Weiting., ... & Wu, Zhe Bao. (2022). TRIM65 determines the fate of a novel subtype of pituitary neuroendocrine tumors via ubiquitination and degradation of TPIT. Neuro-oncology, 24(8), 1286-1297.
MLA	Yao, Hong,et al."TRIM65 determines the fate of a novel subtype of pituitary neuroendocrine tumors via ubiquitination and degradation of TPIT".Neuro-oncology 24.8(2022):1286-1297.