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

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Fransson, Susanne,1975Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Medical and Clinical Genetics,Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg SE-405 30, Sweden (author)

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

Article/chapterEnglish2012

Publisher, publication year, extent ...

2011-10-24
Nature Publishing Group,2012
printrdacarrier

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LIBRIS-ID:oai:DiVA.org:his-5829
https://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-5829URI
https://doi.org/10.1038/onc.2011.492DOI
https://gup.ub.gu.se/publication/151039URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
p110δ
p37δ
p85
RAS
ovarian cancer
colorectal cancer
Natural sciences
Naturvetenskap
cancer
tumörbiologi
molecylärbiologi

Added entries (persons, corporate bodies, meetings, titles ...)

Uv, Anne,1967Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics,Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg SE-405 30, Sweden(Swepub:gu)xuvanz (author)
Eriksson, H.Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics,Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg SE-405 30, Sweden (author)
Andersson, Mattias K,1979Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Pathology,Department of Pathology, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden(Swepub:gu)xamatx (author)
Wettergren, Yvonne,1957Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery,Department of General Surgery, University of Gothenburg SE-40530 Gothenburg, Sweden(Swepub:gu)xwetyv (author)
Bergö, Martin,1970Gothenburg University,Göteborgs universitet,Institutionen för medicin,Sahlgrenska Cancer Center,Institute of Medicine,Department of Medicine, Sahlgrenska Cancer Center, University of Gothenburg, SE-40530 Gothenburg, Sweden(Swepub:gu)xbmarl (author)
Ejeskär, KatarinaGothenburg University,Göteborgs universitet,Högskolan i Skövde,Institutionen för vård och natur,Forskningscentrum för Systembiologi,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics(Swepub:gu)xejeka (author)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik (creator_code:org_t)

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In:Oncogene: Nature Publishing Group31:27, s. 3277-32860950-92321476-5594

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