A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation Journal Article
| Authors: | Drozdz, M. M.; Doane, A. S.; Alkallas, R.; Desman, G.; Bareja, R.; Reilly, M.; Bang, J.; Yusupova, M.; You, J.; Eraslan, Z.; Wang, J. Z.; Verma, A.; Aguirre, K.; Kane, E.; Watson, I. R.; Elemento, O.; Piskounova, E.; Merghoub, T.; Zippin, J. H. |
| Article Title: | A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation |
| Abstract: | Cyclic AMP (cAMP) signaling is localized to multiple spatially distinct microdomains, but the role of cAMP microdomains in cancer cell biology is poorly understood. Here, we present a tunable genetic system that allows us to activate cAMP signaling in specific microdomains. We uncover a nuclear cAMP microdomain that activates a tumor-suppressive pathway in a broad range of cancers by inhibiting YAP, a key effector protein of the Hippo pathway, inside the nucleus. We show that nuclear cAMP induces a LATS-dependent pathway leading to phosphorylation of nuclear YAP solely at serine 397 and export of YAP from the nucleus with no change in YAP protein stability. Thus, nuclear cAMP inhibition of nuclear YAP is distinct from other known mechanisms of Hippo regulation. Pharmacologic targeting of specific cAMP microdomains remains an untapped therapeutic approach for cancer; thus, drugs directed at the nuclear cAMP microdomain may provide avenues for the treatment of cancer. © 2022 The Author(s) |
| Keywords: | neoplasm; neoplasms; metabolism; serine; cell line; phosphorylation; cyclic amp; tumor suppression; hippo pathway; pka; yap; hippo signaling pathway; camp; nucleus; humans; human; hippo signaling; sac; cp: molecular biology; protein serine-threonine kinases; long acting thyroid stimulator; long-acting thyroid stimulator |
| Journal Title: | Cell Reports |
| Volume: | 40 |
| Issue: | 13 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2022-09-27 |
| Start Page: | 111412 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2022.111412 |
| PUBMED: | 36170819 |
| PROVIDER: | scopus |
| PMCID: | PMC9549417 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2022 -- Source: Scopus |
