The NFIB/CARM1 Partnership Is a Driver in Preclinical Models of Small Cell Lung Cancer.

Authors

Guozhen Gao
Simone Hausmann
Natasha M Flores
Ana Morales Benitez
Jianjun Shen
Xiaojie Yang
Maria D Person
Sitaram Gayatri
Donghang Cheng
Yue Lu
Bin Liu
Pawel K Mazur
Mark T Bedford

Publication Date

1-23-2023

Journal

Nature Communications

Abstract

The coactivator associated arginine methyltransferase (CARM1) promotes transcription, as its name implies. It does so by modifying histones and chromatin bound proteins. We identified nuclear factor I B (NFIB) as a CARM1 substrate and show that this transcription factor utilizes CARM1 as a coactivator. Biochemical studies reveal that tripartite motif 29 (TRIM29) is an effector molecule for methylated NFIB. Importantly, NFIB harbors both oncogenic and metastatic activities, and is often overexpressed in small cell lung cancer (SCLC). Here, we explore the possibility that CARM1 methylation of NFIB is important for its transforming activity. Using a SCLC mouse model, we show that both CARM1 and the CARM1 methylation site on NFIB are critical for the rapid onset of SCLC. Furthermore, CARM1 and methylated NFIB are responsible for maintaining similar open chromatin states in tumors. Together, these findings suggest that CARM1 might be a therapeutic target for SCLC.

Keywords

Animals, Mice, NFI Transcription Factors, Small Cell Lung Carcinoma, Protein-Arginine N-Methyltransferases, Chromatin, Lung Neoplasms

Comments

Supplementary Materials

PMID: 36690626