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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| Language: | English |
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Public Library of Science (PLoS)
2021-10-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001085&type=printable |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-bf77b2f3063744f99c20e43fed4301ca |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2021-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-bf77b2f3063744f99c20e43fed4301ca2025-01-18T05:30:40ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852021-10-011910e300108510.1371/journal.pbio.3001085The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.Patrick A CarrollBrian W FreiePei Feng ChengSivakanthan KasinathanHaiwei GuTheresa HedrichJames A DowdleVivek VenkataramaniVijay RamaniXiaoying WuDaniel RafteryJay ShendureDonald E AyerCharles H MullerRobert N EisenmanMale 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).https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001085&type=printable |
| spellingShingle | 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. PLoS Biology |
| title | 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_short | 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 |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001085&type=printable |
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