p37delta is a new isoform of PI3K p110delta that increases cell proliferation and is overexpressed in tumors.
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Fransson S, Uv A, Eriksson H, Andersson MK, Wettergren Y, Bergo M, Ejeskar K
p37delta is a new isoform of PI3K p110delta that increases cell proliferation and is overexpressed in tumors.
Oncogene. 2012 Jul 5;31(27):3277-86. doi: 10.1038/onc.2011.492. Epub 2011 Oct 24.
- PubMed ID
- 22020336 [ View in PubMed]
- Abstract
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 p110delta 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, p37delta, and demonstrate that this protein is expressed in human ovarian and colorectal tumors. p37delta 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 p110delta, which stabilizes p85, p37delta promoted p85 sequestering. Despite the truncated RAS-binding domain, p37delta bound to RAS and we found a strong positive correlation between the protein levels of p37delta and RAS. Overexpressing p37delta, but not p110delta, increased the proliferation and invasive properties of HEK-293 cells and mouse embryonic fibroblasts. Cells overexpressing p37delta showed a quicker phosphorylation response of AKT and ERK1/2 following serum stimulation. Ubiquitous expression of human p37delta in the fruit fly increased body size, DNA content and phosphorylated ERK1/2 levels. Thus, p37delta appears to be a new tumor-specific isoform of p110delta with growth-promoting properties.