Phosphatase of regenerating liver 2 (PRL2) is essential for placental development by down-regulating PTEN (phosphatase and tensin homologue deleted on chromosome 10) and activating Akt protein

Yuanshu Dong, Lujuan Zhang, Sheng Zhang, Yunpeng Bai, Hanying Chen, Xiaoxin Sun, Weidong Yong, Wei Li, Stephanie C. Colvin, Simon Rhodes, Weinian Shou, Zhong-Yin Zhang

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The PRL (phosphatase of regenerating liver) phosphatases are implicated in the control of cell proliferation and invasion. Aberrant PRL expression is associated with progression and metastasis of multiple cancers. However, the specific in vivo function of the PRLs remains elusive. Here we show that deletion of PRL2, the most ubiquitously expressed PRL family member, leads to impaired placental development and retarded growth at both embryonic and adult stages. Ablation of PRL2 inactivates Akt and blocks glycogen cell proliferation, resulting in reduced spongiotrophoblast and decidual layers in the placenta. These structural defects cause placental hypotrophy and insufficiency, leading to fetal growth retardation. We demonstrate that the tumor suppressor PTEN is elevated in PRL2-deficient placenta. Biochemical analyses indicate that PRL2 promotes Akt activation by down-regulating PTEN through the proteasome pathway. This study provides the first evidence that PRL2 is required for extra-embryonic development and associates the oncogenic properties of PRL2 with its ability to negatively regulate PTEN, thereby activating the PI3K-Akt pathway.

Original languageEnglish
Pages (from-to)32172-32179
Number of pages8
JournalJournal of Biological Chemistry
Volume287
Issue number38
DOIs
StatePublished - Sep 14 2012

Fingerprint

PTEN Phosphohydrolase
Placentation
Chromosomes, Human, Pair 10
Chromosomes
Phosphoric Monoester Hydrolases
Liver
Proteins
Cell proliferation
Placenta
Cell Proliferation
Tensins
Placental Insufficiency
Aptitude
Fetal Growth Retardation
Proteasome Endopeptidase Complex
Ablation
Glycogen
Phosphatidylinositol 3-Kinases
Embryonic Development
Tumors

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Phosphatase of regenerating liver 2 (PRL2) is essential for placental development by down-regulating PTEN (phosphatase and tensin homologue deleted on chromosome 10) and activating Akt protein. / Dong, Yuanshu; Zhang, Lujuan; Zhang, Sheng; Bai, Yunpeng; Chen, Hanying; Sun, Xiaoxin; Yong, Weidong; Li, Wei; Colvin, Stephanie C.; Rhodes, Simon; Shou, Weinian; Zhang, Zhong-Yin.

In: Journal of Biological Chemistry, Vol. 287, No. 38, 14.09.2012, p. 32172-32179.

Research output: Contribution to journalArticle

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abstract = "The PRL (phosphatase of regenerating liver) phosphatases are implicated in the control of cell proliferation and invasion. Aberrant PRL expression is associated with progression and metastasis of multiple cancers. However, the specific in vivo function of the PRLs remains elusive. Here we show that deletion of PRL2, the most ubiquitously expressed PRL family member, leads to impaired placental development and retarded growth at both embryonic and adult stages. Ablation of PRL2 inactivates Akt and blocks glycogen cell proliferation, resulting in reduced spongiotrophoblast and decidual layers in the placenta. These structural defects cause placental hypotrophy and insufficiency, leading to fetal growth retardation. We demonstrate that the tumor suppressor PTEN is elevated in PRL2-deficient placenta. Biochemical analyses indicate that PRL2 promotes Akt activation by down-regulating PTEN through the proteasome pathway. This study provides the first evidence that PRL2 is required for extra-embryonic development and associates the oncogenic properties of PRL2 with its ability to negatively regulate PTEN, thereby activating the PI3K-Akt pathway.",
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AU - Bai, Yunpeng

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AU - Sun, Xiaoxin

AU - Yong, Weidong

AU - Li, Wei

AU - Colvin, Stephanie C.

AU - Rhodes, Simon

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AU - Zhang, Zhong-Yin

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