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p37δ is a new isoform of PI3K p110δ that increases cell proliferation and is overexpressed in tumors.

Journal article
Authors Susanne Fransson
Anne Uv
Henry Eriksson
Mattias K Andersson
Yvonne Wettergren
Martin Bergö
Katarina Ejeskär
Published in Oncogene
Volume 31
Issue 27
Pages 3277-86
ISSN 1476-5594
Publication year 2012
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Institute of Clinical Sciences, Department of Surgery
Sahlgrenska Cancer Center
Institute of Biomedicine, Department of Pathology
Institute of Medicine
Pages 3277-86
Language en
Keywords cancer, tumörbiologi, molecylärbiologi
Subject categories Medical cell biology, Molecular medicine


The phosphatidylinositol 3-kinases (PI3Ks) regulate cell growth, proliferation and survival, and are frequently affected in human cancer. PI3K is composed of a catalytic subunit, p110, and a regulatory subunit, p85. The PI3K catalytic subunit p110δ is encoded by PIK3CD and contains p85- and RAS-binding domains, and a kinase domain. Here we present an alternatively spliced PIK3CD transcript encoding a previously unknown protein, p37δ, and demonstrate that this protein is expressed in human ovarian and colorectal tumors. p37δ retains the p85-binding domain and a fraction of the RAS-binding domain, lacks the catalytic domain, and has a unique carboxyl-terminal region. In contrast to p110δ, which stabilizes p85, p37δ promoted p85 sequestering. Despite the truncated RAS-binding domain, p37δ bound to RAS and we found a strong positive correlation between the protein levels of p37δ and RAS. Overexpressing p37δ, but not p110δ, increased the proliferation and invasive properties of HEK-293 cells and mouse embryonic fibroblasts. Cells overexpressing p37δ showed a quicker phosphorylation response of AKT and ERK1/2 following serum stimulation. Ubiquitous expression of human p37δ in the fruit fly increased body size, DNA content and phosphorylated ERK1/2 levels. Thus, p37δ appears to be a new tumor-specific isoform of p110δ with growth-promoting properties.Oncogene advance online publication, 24 October 2011; doi:10.1038/onc.2011.492.

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