Acetylation of ELMO1 correlates with Rac1 activity and colorectal cancer progress

Chuangkun Li; Jianmei Yi; Haiqing Jie; Zhihang Liu; Shujuan Li; Ziwei Zeng; Yi Zhou

doi:10.1016/j.yexcr.2024.114068

Acetylation of ELMO1 correlates with Rac1 activity and colorectal cancer progress

Exp Cell Res. 2024 May 13;439(1):114068. doi: 10.1016/j.yexcr.2024.114068. Online ahead of print.

Authors

Chuangkun Li¹, Jianmei Yi¹, Haiqing Jie², Zhihang Liu³, Shujuan Li⁴, Ziwei Zeng², Yi Zhou⁵

Affiliations

¹ Department of General Surgery, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Hunan, China.
² Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
³ The "Double-First Class" Application Characteristic Discipline of Hunan Province (Clinical Medicine), Changsha Medical University, Changsha, China.
⁴ Department of Pharmacy, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁵ Department of General Surgery, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Hunan, China. Electronic address: 15802522868@163.com.

PMID: 38750717
DOI: 10.1016/j.yexcr.2024.114068

Abstract

Acetylation, a critical regulator of diverse cellular processes, holds significant implications in various cancer contexts. Further understanding of the acetylation patterns of key cancer-driven proteins is crucial for advancing therapeutic strategies in cancer treatment. This study aimed to unravel the acetylation patterns of Engulfment and Cell Motility Protein 1 (ELMO1) and its relevance to the pathogenesis of colorectal cancer (CRC). Immunoprecipitation and mass spectrometry precisely identified lysine residue 505 (K505) as a central acetylation site in ELMO1. P300 emerged as the acetyltransferase for ELMO1 K505 acetylation, while SIRT2 was recognized as the deacetylase. Although K505 acetylation minimally affected ELMO1's localization and stability, it played a crucial role in mediating ELMO1-Dock180 interaction, thereby influencing Rac1 activation. Functionally, ELMO1 K505 acetylation proved to be a pivotal factor in CRC progression, exerting its influence on key cellular processes. Clinical analysis of CRC samples unveiled elevated ELMO1 acetylation in primary tumors, indicating a potential association with CRC pathologies. This work provides insights into ELMO1 acetylation and its significance in advancing potentially therapeutic interventions in CRC treatment.

Keywords: Acetylation; Colorectal cancer; ELMO1.