CRTC, not phosphorylated CREB1, mediates cAMP-induced transcription across diverse cell types

CRTC versus phosphorylated CREB1: key claim

The title of the preprint states that CRTC, not phosphorylated CREB1, is responsible for driving cAMP-induced transcription across diverse cell types. This framing challenges the commonly cited model that phosphorylation of CREB1 is the central molecular event mediating cAMP-responsive gene activation, and instead highlights CRTC as the dominant effector according to the authors' report.

Preprint status and authorship

This work is posted on bioRxiv as a preprint and has not undergone peer review. The manuscript lists multiple authors, primarily affiliated with Massachusetts General Hospital and associated institutions. The author list includes Charles H. Adelmann, Michelle Liu, Allison E. Greuel, Lingjuan Huang, Judith R. Boozer, Avanthika Venkatachalam, Xunwei Wu, Eleanor Ziarnik, Jiayin Tang, Ana Clara Morellato Alcantara, Joshua P. Carreras, Suyeon Ryu, Charles Shi, Long Huynh, Tristan Vornbaeumen, Garyfallia Papaioannou, David S.B. Hoon, Nir Hacohen, Marc N. Wein, and David E. Fisher. The preprint DOI is provided on the bioRxiv record.

Background context implied by the title

The title implies a reassessment of signal-dependent transcriptional control in response to cAMP signalling, emphasizing CRTC as the principal transcriptional driver rather than phosphorylated CREB1. The claim, as stated, applies to multiple and varied cell types, suggesting the authors believe the observation is broadly generalizable across cellular contexts.

What the provided source text reports (explicit facts)

• The source excerpt supplied to this summary contains the article title, full author list, affiliations, and the statement that the article is a preprint not certified by peer review.
• The central assertion available from the supplied content is the article title: that CRTC, not phosphorylated CREB1, drives cAMP-induced transcription across diverse cell types.

No additional experimental descriptions, results, figures, quantitative data, or specific gene targets are included in the provided excerpt.

Missing details and limitations of the source excerpt

The content provided does not include the manuscript abstract, introduction, methods, results, figures, or discussion sections. Consequently, the following were not reported in the supplied source material and cannot be summarized or confirmed here:

• Specific experimental approaches and assays used (for example, whether the authors used RNA-seq, reporter assays, chromatin immunoprecipitation, CRISPR perturbations, imaging, biochemical fractionation, or other techniques).
• The identity and number of the "diverse cell types" examined, and whether they span tissues, primary cells, or cell lines.
• Quantitative results, statistical analyses, or effect sizes supporting the title claim.
• The direct molecular evidence attributing transcriptional control to CRTC rather than phosphorylated CREB1 (for example, loss- or gain-of-function experiments, localization studies, or binding assays).
• Any broader functional consequences, physiological contexts, or disease relevance described by the authors.

Because these details are absent from the provided excerpt, no further factual claims about the study design or findings can be made here without consulting the full preprint.

Potential implications and cautions for researchers

If substantiated by the full dataset and peer review, the claim that CRTC is the primary driver of cAMP-induced transcription across cell types would have implications for basic research on cAMP signalling and for fields that target CREB/CRTC pathways. However, the version of the article available in the provided content is a preprint; as such, all conclusions are provisional until the work is evaluated through peer review and until the underlying data and methods are examined.

Researchers interested in this topic should review the complete preprint for experimental detail and assess the evidence directly before integrating the conclusion into experimental designs or translational work. Important questions to evaluate in the full text include which cell types were tested, the experimental perturbations employed, whether causality was demonstrated, and how broadly the results generalize.

Where to find the full report and next steps

The full preprint is hosted on bioRxiv and is identified by the DOI shown in the article header. To evaluate the claim comprehensively, readers should access the complete preprint on bioRxiv to read the abstract, methods, results, and figures. Subsequent peer-reviewed publication, replication by independent groups, and detailed methodological review will be important steps to confirm and contextualize the reported finding.

Note: This rewritten summary is restricted to facts and items explicitly present in the source excerpt supplied. Detailed experimental results, numeric findings, and specific mechanistic data were not included in the provided content and therefore are not reported here.