FBL promotes cancer cell resistance to DNA damage and BRCA1 transcription via YBX1

被引：17

作者：

Sun, Xiaorui ^{[1
]}

Gao, Congwen ^{[1
]}

Xu, Xin ^{[1
]}

Li, Mengyuan ^{[1
]}

Zhao, Xinhua ^{[1
]}

Wang, Yanan ^{[2
]}

Wang, Yun ^{[2
]}

Zhang, Shun ^{[2
]}

Yan, Zhenzhen ^{[1
]}

Liu, Xiuhua ^{[1
]}

Wu, Chen ^{[1
,3
]}

机构：

[1] Hebei Univ, Coll Life Sci, Baoding, Peoples R China

[2] Hebei Univ, Affiliated Hosp, Baoding, Peoples R China

[3] Hebei Univ, Key Lab Zool Systemat & Applicat, Baoding, Peoples R China

来源：

EMBO REPORTS | 2023年 / 24卷 / 09期

基金：

中国国家自然科学基金;

关键词：

FBL; DNA damage repair; YBX1; BRCA1; colon cancer; BOX-BINDING-PROTEIN; RIBOSOMAL-RNA METHYLATION; HUMAN FIBRILLARIN; YB-1; REPAIR; GENE; CISPLATIN; SENSITIVITY; ACTIVATION; REGULATOR;

D O I：

10.15252/embr.202256230

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fibrillarin (FBL) is a highly conserved nucleolar methyltransferase responsible for methylation of ribosomal RNA and proteins. Here, we reveal a role for FBL in DNA damage response and its impact on cancer proliferation and sensitivity to DNA-damaging agents. FBL is highly expressed in various cancers and correlates with poor survival outcomes in cancer patients. Knockdown of FBL sensitizes tumor cells and xenografts to DNA crosslinking agents, and leads to homologous recombination-mediated DNA repair defects. We identify Y-box-binding protein-1 (YBX1) as a key interacting partner of FBL, and FBL increases the nuclear accumulation of YBX1 in response to DNA damage. We show that FBL promotes the expression of BRCA1 by increasing the binding of YBX1 to the BRCA1 promoter. Our study sheds light on the regulatory mechanism of FBL in tumorigenesis and DNA damage response, providing potential therapeutic targets to overcome chemoresistance in cancer.

引用

页数：18

共 52 条

[1] CDNA CLONING AND SEQUENCING OF HUMAN FIBRILLARIN, A CONSERVED NUCLEOLAR PROTEIN RECOGNIZED BY AUTOIMMUNE ANTISERA [J].