TY - JOUR
T1 - PNUTS functions as a proto-oncogene by sequestering PTEN
AU - Kavela, Sridhar
AU - Shinde, Swapnil R.
AU - Ratheesh, Raman
AU - Viswakalyan, Kotapalli
AU - Bashyam, Murali D.
AU - Gowrishankar, Swarnalata
AU - Vamsy, Mohana
AU - Pattnaik, Sujit
AU - Rao, Subramanyeshwar
AU - Sastry, Regulagadda A.
AU - Srinivasulu, Mukta
AU - Chen, Junjie
AU - Maddika, Subbareddy
PY - 2013/1/1
Y1 - 2013/1/1
N2 - PTEN is a well-defined tumor suppressor gene that antagonizes the PI3K/Akt pathway to regulate a multitude of cellular processes, such as survival, growth, motility, invasiveness, and angiogenesis. While the functions of PTEN have been studied extensively, the regulation of its activity during normal and disease conditions still remains incompletely understood. In this study, we identified the protein phosphatase-1 nuclear targeting subunit PNUTS (PPP1R10) as a PTEN-associated protein. PNUTS directly interacted with the lipid-binding domain (C2 domain) of PTEN and sequestered it in the nucleus. Depletion of PNUTS leads to increased apoptosis and reduced cellular proliferation in a PTEN-dependent manner. PNUTS expression was elevated in certain cancers compared with matched normal tissues. Collectively, our studies reveal PNUTS as a novel PTEN regulator and a likely oncogene.
AB - PTEN is a well-defined tumor suppressor gene that antagonizes the PI3K/Akt pathway to regulate a multitude of cellular processes, such as survival, growth, motility, invasiveness, and angiogenesis. While the functions of PTEN have been studied extensively, the regulation of its activity during normal and disease conditions still remains incompletely understood. In this study, we identified the protein phosphatase-1 nuclear targeting subunit PNUTS (PPP1R10) as a PTEN-associated protein. PNUTS directly interacted with the lipid-binding domain (C2 domain) of PTEN and sequestered it in the nucleus. Depletion of PNUTS leads to increased apoptosis and reduced cellular proliferation in a PTEN-dependent manner. PNUTS expression was elevated in certain cancers compared with matched normal tissues. Collectively, our studies reveal PNUTS as a novel PTEN regulator and a likely oncogene.
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U2 - 10.1158/0008-5472.CAN-12-1394
DO - 10.1158/0008-5472.CAN-12-1394
M3 - Article
C2 - 23117887
AN - SCOPUS:84872001794
SN - 0008-5472
VL - 73
SP - 205
EP - 214
JO - Cancer Research
JF - Cancer Research
IS - 1
ER -