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Nat Commun January 1, 2019; 10 (1): 3960.

Pituitary cell translation and secretory capacities are enhanced cell autonomously by the transcription factor Creb3l2.

Khetchoumian K , Balsalobre A , Mayran A , Christian H , Chénard V , St-Pierre J , Drouin J .

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.

PubMed ID: 31481663
PMC ID: PMC6722061
Article link: Nat Commun
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: creb3l2 crh homer1 kcnma1 mtor pdx1 pomc prdm1 rps6ka3 ssr3 tbp thibz xbp1

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References [+] :
, Expansion of the Gene Ontology knowledgebase and resources. 2017, Pubmed