2. Academic Validation
  3. Sirtuin5 protects colorectal cancer from DNA damage by keeping nucleotide availability

Sirtuin5 protects colorectal cancer from DNA damage by keeping nucleotide availability

  • Nat Commun. 2022 Oct 17;13(1):6121. doi: 10.1038/s41467-022-33903-8.
Hao-Lian Wang # 1,  Yan Chen # 1,  Yun-Qian Wang # 1,  En-Wei Tao 1,  Juan Tan 1,  Qian-Qian Liu 1,  Chun-Min Li 1,  Xue-Mei Tong 2,  Qin-Yan Gao 1,  Jie Hong 1,  Ying-Xuan Chen 3,  Jing-Yuan Fang 1
Affiliations

Affiliations

  • 1 State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 2 Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. yingxuanchen71@sjtu.edu.cn.
  • # Contributed equally.
PMID: 36253417 DOI: 10.1038/s41467-022-33903-8
Abstract

In our previous study, we reported that sirtuin5 (SIRT5), a member of the NAD+-dependent class III histone deacetylase family, is highly expressed in colorectal Cancer (CRC). Herein we show that SIRT5 knockdown impairs the production of ribose-5-phosphate, which is essential for nucleotide synthesis, resulting in continuous and irreparable DNA damage and consequently leading to cell cycle arrest and enhanced Apoptosis in CRC cells. These SIRT5 silencing-induced effects can be reversed by nucleoside supplementation. Mechanistically, SIRT5 activates Transketolase (TKT), a key Enzyme in the non-oxidative pentose phosphate pathway, in a demalonylation-dependent manner. Furthermore, TKT is essential for SIRT5-induced malignant phenotypes of CRC both in vivo and in vitro. Altogether, SIRT5 silencing induces DNA damage in CRC via post-translational modifications and inhibits tumor growth, suggesting that SIRT5 can serve as a promising target for CRC treatment.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z