The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.

Male germ cell (GC) production is a metabolically driven and apoptosis-prone process. Here, we show that the glucose-sensing transcription factor (TF) MAX-Like protein X (MLX) and its binding partner MondoA are both required for male fertility in the mouse, as well as survival of human tumor cells d...

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Autores principales:	Patrick A Carroll, Brian W Freie, Pei Feng Cheng, Sivakanthan Kasinathan, Haiwei Gu, Theresa Hedrich, James A Dowdle, Vivek Venkataramani, Vijay Ramani, Xiaoying Wu, Daniel Raftery, Jay Shendure, Donald E Ayer, Charles H Muller, Robert N Eisenman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bf77b2f3063744f99c20e43fed4301ca
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spelling	oai:doaj.org-article:bf77b2f3063744f99c20e43fed4301ca2021-11-25T05:34:15ZThe glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.1544-91731545-788510.1371/journal.pbio.3001085https://doaj.org/article/bf77b2f3063744f99c20e43fed4301ca2021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001085https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Male germ cell (GC) production is a metabolically driven and apoptosis-prone process. Here, we show that the glucose-sensing transcription factor (TF) MAX-Like protein X (MLX) and its binding partner MondoA are both required for male fertility in the mouse, as well as survival of human tumor cells derived from the male germ line. Loss of Mlx results in altered metabolism as well as activation of multiple stress pathways and GC apoptosis in the testes. This is concomitant with dysregulation of the expression of male-specific GC transcripts and proteins. Our genomic and functional analyses identify loci directly bound by MLX involved in these processes, including metabolic targets, obligate components of male-specific GC development, and apoptotic effectors. These in vivo and in vitro studies implicate MLX and other members of the proximal MYC network, such as MNT, in regulation of metabolism and differentiation, as well as in suppression of intrinsic and extrinsic death signaling pathways in both spermatogenesis and male germ cell tumors (MGCTs).Patrick A CarrollBrian W FreiePei Feng ChengSivakanthan KasinathanHaiwei GuTheresa HedrichJames A DowdleVivek VenkataramaniVijay RamaniXiaoying WuDaniel RafteryJay ShendureDonald E AyerCharles H MullerRobert N EisenmanPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 10, p e3001085 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Patrick A Carroll Brian W Freie Pei Feng Cheng Sivakanthan Kasinathan Haiwei Gu Theresa Hedrich James A Dowdle Vivek Venkataramani Vijay Ramani Xiaoying Wu Daniel Raftery Jay Shendure Donald E Ayer Charles H Muller Robert N Eisenman The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.
description	Male germ cell (GC) production is a metabolically driven and apoptosis-prone process. Here, we show that the glucose-sensing transcription factor (TF) MAX-Like protein X (MLX) and its binding partner MondoA are both required for male fertility in the mouse, as well as survival of human tumor cells derived from the male germ line. Loss of Mlx results in altered metabolism as well as activation of multiple stress pathways and GC apoptosis in the testes. This is concomitant with dysregulation of the expression of male-specific GC transcripts and proteins. Our genomic and functional analyses identify loci directly bound by MLX involved in these processes, including metabolic targets, obligate components of male-specific GC development, and apoptotic effectors. These in vivo and in vitro studies implicate MLX and other members of the proximal MYC network, such as MNT, in regulation of metabolism and differentiation, as well as in suppression of intrinsic and extrinsic death signaling pathways in both spermatogenesis and male germ cell tumors (MGCTs).
format	article
author	Patrick A Carroll Brian W Freie Pei Feng Cheng Sivakanthan Kasinathan Haiwei Gu Theresa Hedrich James A Dowdle Vivek Venkataramani Vijay Ramani Xiaoying Wu Daniel Raftery Jay Shendure Donald E Ayer Charles H Muller Robert N Eisenman
author_facet	Patrick A Carroll Brian W Freie Pei Feng Cheng Sivakanthan Kasinathan Haiwei Gu Theresa Hedrich James A Dowdle Vivek Venkataramani Vijay Ramani Xiaoying Wu Daniel Raftery Jay Shendure Donald E Ayer Charles H Muller Robert N Eisenman
author_sort	Patrick A Carroll
title	The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.
title_short	The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.
title_full	The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.
title_fullStr	The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.
title_full_unstemmed	The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.
title_sort	glucose-sensing transcription factor mlx balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/bf77b2f3063744f99c20e43fed4301ca
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The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.

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