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

Nat Commun. 2019 Sep 3;10(1):3960. doi: 10.1038/s41467-019-11894-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Cell Differentiation / physiology
  • Cell Line
  • Endoplasmic Reticulum / genetics
  • Gene Expression Regulation
  • Homeodomain Proteins / genetics
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pituitary Gland / cytology
  • Pituitary Gland / metabolism*
  • Pro-Opiomelanocortin / metabolism
  • Signal Transduction
  • T-Box Domain Proteins / genetics
  • X-Box Binding Protein 1 / metabolism
  • Xenopus laevis


  • Basic-Leucine Zipper Transcription Factors
  • Creb3l2 protein, mouse
  • Homeodomain Proteins
  • T-Box Domain Proteins
  • Tbx19 protein, mouse
  • X-Box Binding Protein 1
  • Xbp1 protein, mouse
  • Pro-Opiomelanocortin