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Review

The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis

1
Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
2
Institute of Chemical Biology, Department of Chemistry, Imperial College London, London W12 0BZ, UK
3
Developmental Dynamics, National Heart and Lung Institute (NHLI), Imperial College London, Imperial Center of Translational and Experimental Medicine, London W12 0NN, UK
*
Author to whom correspondence should be addressed.
Cells 2019, 8(12), 1594; https://doi.org/10.3390/cells8121594
Received: 15 November 2019 / Revised: 5 December 2019 / Accepted: 5 December 2019 / Published: 7 December 2019
(This article belongs to the Special Issue New Advances in Cyclic AMP Signalling)
The Popeye domain containing (POPDC) gene family consists of POPDC1 (also known as BVES), POPDC2 and POPDC3 and encodes a novel class of cyclic adenosine monophosphate (cAMP) effector proteins. Despite first reports of their isolation and initial characterization at the protein level dating back 20 years, only recently major advances in defining their biological functions and disease association have been made. Loss-of-function experiments in mice and zebrafish established an important role in skeletal muscle regeneration, heart rhythm control and stress signaling. Patients suffering from muscular dystrophy and atrioventricular block were found to carry missense and nonsense mutations in either of the three POPDC genes, which suggests an important function in the control of striated muscle homeostasis. However, POPDC genes are also expressed in a number of epithelial cells and function as tumor suppressor genes involved in the control of epithelial structure, tight junction formation and signaling. Suppression of POPDC genes enhances tumor cell proliferation, migration, invasion and metastasis in a variety of human cancers, thus promoting a malignant phenotype. Moreover, downregulation of POPDC1 and POPDC3 expression in different cancer types has been associated with poor prognosis. However, high POPDC3 expression has also been correlated to poor clinical prognosis in head and neck squamous cell carcinoma, suggesting that POPDC3 potentially plays different roles in the progression of different types of cancer. Interestingly, a gain of POPDC1 function in tumor cells inhibits cell proliferation, migration and invasion thereby reducing malignancy. Furthermore, POPDC proteins have been implicated in the control of cell cycle genes and epidermal growth factor and Wnt signaling. Work in tumor cell lines suggest that cyclic nucleotide binding may also be important in epithelial cells. Thus, POPDC proteins have a prominent role in tissue homeostasis and cellular signaling in both epithelia and striated muscle. View Full-Text
Keywords: cyclic adenosine monophosphate (cAMP); signaling; membrane trafficking; cardiac arrhythmia; muscular dystrophy; adhesion; cancer; cell proliferation; migration; invasion cyclic adenosine monophosphate (cAMP); signaling; membrane trafficking; cardiac arrhythmia; muscular dystrophy; adhesion; cancer; cell proliferation; migration; invasion
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MDPI and ACS Style

Amunjela, J.N.; Swan, A.H.; Brand, T. The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis. Cells 2019, 8, 1594. https://doi.org/10.3390/cells8121594

AMA Style

Amunjela JN, Swan AH, Brand T. The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis. Cells. 2019; 8(12):1594. https://doi.org/10.3390/cells8121594

Chicago/Turabian Style

Amunjela, Johanna N., Alexander H. Swan, and Thomas Brand. 2019. "The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis" Cells 8, no. 12: 1594. https://doi.org/10.3390/cells8121594

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