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Pituitary cell translation and secretory capacities are enhanced cell autonomously by the transcription factor Creb3l2
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Pituitary cell translation and secretory capacities are enhanced cell autonomously by the transcription factor Creb3l2
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Journal Article
Pituitary cell translation and secretory capacities are enhanced cell autonomously by the transcription factor Creb3l2
2019
Overview
Translation is a basic cellular process and its capacity is adapted to cell function. In particular, secretory cells achieve high protein synthesis levels without triggering the protein stress response. It is unknown how and when translation capacity is increased during differentiation. Here, we show that the transcription factor Creb3l2 is a scaling factor for translation capacity in pituitary secretory cells and that it directly binds ~75% of regulatory and effector genes for translation. In parallel with this cell-autonomous mechanism, implementation of the physiological UPR pathway prevents triggering the protein stress response. Knockout mice for
Tpit
, a pituitary differentiation factor, show that Creb3l2 expression and its downstream regulatory network are dependent on
Tpit
. Further, Creb3l2 acts by direct targeting of translation effector genes in parallel with signaling pathways that otherwise regulate protein synthesis. Expression of Creb3l2 may be a useful means to enhance production of therapeutic proteins.
Pituitary POMC secreting cells achieve high hormone expression levels after birth but the mechanism for this regulation is unclear. Here, the authors show that this process is driven cell autonomously by the differentiation factor Tpit that activates the bZIP transcription factors Creb3l2 and XBP1 to enhance translation and secretory capacities.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/109
/ 13/51
/ 38/109
/ 38/15
/ 38/39
/ 38/88
/ 64/110
/ 64/114
/ 64/60
/ Animals
/ Basic-Leucine Zipper Transcription Factors - genetics
/ Basic-Leucine Zipper Transcription Factors - metabolism
/ Cell Differentiation - physiology
/ Endoplasmic Reticulum - genetics
/ Genes
/ Homeodomain Proteins - genetics
/ Humanities and Social Sciences
/ Pituitary Gland - metabolism
/ Pro-Opiomelanocortin - metabolism
/ Proteins
/ Scaling
/ Science
/ T-Box Domain Proteins - genetics
