The NFIB/CARM1 partnership is a driver in preclinical models of small cell lung cancer

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

doi:10.1038/s41467-023-35864-y

The NFIB/CARM1 partnership is a driver in preclinical models of small cell lung cancer

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

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10 Scopus citations

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.

Original language	English (US)
Article number	363
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-35864-y
State	Published - Dec 2023

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

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10.1038/s41467-023-35864-y

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@article{74416423ffac4a618a79b7d2f5202219,

title = "The NFIB/CARM1 partnership is a driver in preclinical models of small cell lung cancer",

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.",

author = "Guozhen Gao and Simone Hausmann and Flores, {Natasha M.} and Benitez, {Ana Morales} and Jianjun Shen and Xiaojie Yang and Person, {Maria D.} and Sitaram Gayatri and Donghang Cheng and Yue Lu and Bin Liu and Mazur, {Pawel K.} and Bedford, {Mark T.}",

note = "Funding Information: This work was supported in part by grants from the NIH to M.T.B. (GM126421), P.K.M. (R01CA236949 R01CA236118, R01CA266280), S.H. (K99CA255936). P.K.M. is supported by CPRIT (RP220391), AACR, NETRF, DOD PRCRP Career Development Award (CA181486), Career Enhancement Grant - The University of Texas NIH SPORE in Lung Cancer (P50CA070907), the Andrew Sabin Family Foundation Scientist and CPRIT Scholar in Cancer Research (RR160078). We thank Michelle V. Gadush and William Russell for assistance with the mass spec studies, and Vidyasiri Vemulapalli for assistance with the early NFIB-related studies. Protein identification was provided by the UT Austin Center for Biomedfical Research Support Biological Mass Spectrometry Facility (RRID:SCR 0211728) and The Mass Spectrometry Facility at UTMB is supported in part by CPRIT grant number (RP190682). Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-35864-y",

language = "English (US)",

volume = "14",

journal = "Nature communications",

issn = "2041-1723",

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TY - JOUR

T1 - The NFIB/CARM1 partnership is a driver in preclinical models of small cell lung cancer

AU - Gao, Guozhen

AU - Hausmann, Simone

AU - Flores, Natasha M.

AU - Benitez, Ana Morales

AU - Shen, Jianjun

AU - Yang, Xiaojie

AU - Person, Maria D.

AU - Gayatri, Sitaram

AU - Cheng, Donghang

AU - Lu, Yue

AU - Liu, Bin

AU - Mazur, Pawel K.

AU - Bedford, Mark T.

N1 - Funding Information: This work was supported in part by grants from the NIH to M.T.B. (GM126421), P.K.M. (R01CA236949 R01CA236118, R01CA266280), S.H. (K99CA255936). P.K.M. is supported by CPRIT (RP220391), AACR, NETRF, DOD PRCRP Career Development Award (CA181486), Career Enhancement Grant - The University of Texas NIH SPORE in Lung Cancer (P50CA070907), the Andrew Sabin Family Foundation Scientist and CPRIT Scholar in Cancer Research (RR160078). We thank Michelle V. Gadush and William Russell for assistance with the mass spec studies, and Vidyasiri Vemulapalli for assistance with the early NFIB-related studies. Protein identification was provided by the UT Austin Center for Biomedfical Research Support Biological Mass Spectrometry Facility (RRID:SCR 0211728) and The Mass Spectrometry Facility at UTMB is supported in part by CPRIT grant number (RP190682). Publisher Copyright: © 2023, The Author(s).

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-023-35864-y

DO - 10.1038/s41467-023-35864-y

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AN - SCOPUS:85146771374

SN - 2041-1723

VL - 14

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 363

ER -

The NFIB/CARM1 partnership is a driver in preclinical models of small cell lung cancer

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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