Disruption of Serine/Threonine Protein Phosphatase 5 (PP5:PPP5c) in Mice Reveals a Novel Role for PP5 in the Regulation of Ultraviolet Light-induced Phosphorylation of Serine/Threonine Protein Kinase Chk1 (CHEK1)

Amable, Lauren; Grankvist, Nina; Largen, Jason W.; Ortsäter, Henrik; Sjöholm, Åke; Honkanen, Richard E.

doi:10.1074/jbc.m111.244053

Cited by 35 publications

(39 citation statements)

References 48 publications

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“…Our studies on the Ppp5 D274 A 'knockin' (KI) (Ppp5KI) mouse are the first to report the effects of inactivated Ppp5 on GR phosphorylation and differentiation in adipose tissue of an animal model. Homozygous Ppp5KI and PP5KO mice were viable and fertile, but selection against the homozygous male offspring of Ppp5KI heterozygous intercrosses was statistically significant and a similar prenatal effect was observed in one of the KO models [18]. Our genetic analyses further show that there is a trend towards significance for selection against homozygous Ppp5KI female offspring and 13.5-day male/female embryos of Ppp5 D274 A/ + intercrosses.…”

Section: Discussionsupporting

confidence: 50%

“…We demonstrate that preadipocytes expressing inactivated Ppp5 differentiate more slowly in culture than in wild-type preadipocytes and that more stromal cells, which include preadipocytes, are present in the gonadal fat pads of Ppp5 D274A/D274A mice, data which support a block in an early step of preadipocyte differentiation. Two mouse PP5KO models were previously analysed without noting decreased amounts of adipose tissue or biochemical alterations in this tissue [17,18]. Our studies on the Ppp5 D274 A 'knockin' (KI) (Ppp5KI) mouse are the first to report the effects of inactivated Ppp5 on GR phosphorylation and differentiation in adipose tissue of an animal model.…”

Section: Discussionmentioning

confidence: 96%

“…Studies in cell cultures have suggested that Ppp5 is a negative regulator of GR-mediated growth arrest [15] and that Ppp5 may modify the transcriptional profile of the cell [16]. However, analyses of two mouse models [17,18] where the expression of Ppp5/PP5 protein was below detection, termed PP5 'knockout' (KO) (PP5KO), did not report any overt in vivo physiological abnormalities attributed to alteration of GR function. In the present study, we analyse a murine model, in which an inactive Ppp5 replaces the wild-type Ppp5 and leads to changes in GR-mediated fat deposition.…”

Section: Introductionmentioning

confidence: 99%

“…Although some (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). (E) Weight of adipose tissue (fat) dissected from the gonadal and omental fat depots of 7-9-month-old male Ppp5 + / + , Ppp5 D274 A/ + and Ppp5 D274A/D274A mice fed on a standard chow diet and compared with the liver weight.…”

Section: Fat Depots Of Adult Ppp5mentioning

confidence: 99%

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Decreased adipogenesis and adipose tissue in mice with inactivated protein phosphatase 5

Jacob

Rosenzweig

Vázquez-Martin

et al. 2015

Biochemical Journal

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Glucocorticoids play an important role in the treatment of inflammation and immune disorders, despite side effects, which include metabolic derangements such as central adiposity. These studies examine the role of protein phosphatase 5 (Ppp5) in glucocorticoid receptor (GR) complexes which mediate response to glucocorticoids. Mice homozygous for inactivated Ppp5 (Ppp5 D274A/D274A ) exhibit decreased adipose tissue surrounding the gonads and kidneys compared with wild-type mice. Adipocyte size is smaller, more preadipocytes/stromal cell are present in their gonadal fat tissue and differentiation of preadipocytes to adipocytes is retarded. Glucocorticoid levels are raised and the GR is hyperphosphorylated in adipose tissue of Ppp5 D274A/D274A mice at Ser212 and Ser220 (orthologous to human Ser203 and Ser211) in the absence of glucocorticoids. Preadipocyte cultures from Ppp5 D274A/D274A mice show decreased down regulation of Delta-like protein-1/preadipocyte factor-1, hyperphosphorylation of extra-cellular signal regulated kinase 2 (ERK2) and increased concentration of (sex determining region Y)-box 9 (SOX9), changes in a pathway essential for preadipocyte differentiation, which leads to decreased concentrations of the transcription factors CEBPβ and CEBPα necessary for the later stages of adipogenesis. The data indicate that Ppp5 plays a crucial role in modifying GR-mediated initiation of adipose tissue differentiation, suggesting that inhibition of Ppp5 may potentially be beneficial to prevent obesity during glucocorticoid treatment.

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Fat Depots Of Adult Ppp5mentioning

confidence: 99%

See 2 more Smart Citations

Decreased adipogenesis and adipose tissue in mice with inactivated protein phosphatase 5

Jacob

Rosenzweig

Vázquez-Martin

et al. 2015

Biochemical Journal

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“…It has been reported that the overexpression of PPP5C has been observed in several solid cancer types (42)(43)(44). In addition, overexpression of PPP5C has been demonstrated to promote cell proliferation and tumor progression (35).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of serine/threonine protein phosphatase 5 enhances gemcitabine sensitivity by promoting apoptosis in pancreatic cancer cells inï¿½vitro

Zhu

et al. 2018

Oncol Lett

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Abstract. The targeting protein of serine/threonine protein phosphatase 5 (PPP5C) has been reported to be present in various malignancies. However, its functional role in pancreatic cancer (PC) remains unknown. In the present study, the function of PPP5C in PC cells treated with the first-line drug gemcitabine (GEM) was investigated. Short hairpin (sh)RNA targeting PPP5C was constructed to knockdown PPP5C in PANC-1 cells. Cell cycle and apoptosis analyses were performed in order to investigate the mechanisms underlying the effects induced by PPP5C silencing combined with GEM treatment. Western blot analysis was applied to detect the expression of certain key regulators of cell apoptosis in PANC-1 cells treated with GEM. shRNA against PPP5C effectively suppressed the proliferation of PANC-1 cells treated with GEM. Additionally, cell cycle analysis indicated that PPP5C knockdown resulted in a higher number of PANC-1 cells treated with GEM in G 0 /G 1 phase arrest. Knockdown of PPP5C increased the expression of associated apoptotic markers, including cleaved caspase 3, poly (ADP-ribose) polymerase and phosphorylated (p)-p53. In addition, the combination of treatment with GEM and PPP5C silencing significantly increased the apoptosis of PANC-1 cells by affecting the expression levels of p-c-Jun N-terminal kinases and p-p38. The present study suggests that PPP5C may be a potential target for the treatment of PC and that it may enhance the gemcitabine sensitivity of PC cells.

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Serine/threonine protein phosphatase 5 regulates glucose homeostasis in vivo and apoptosis signalling in mouse pancreatic islets and clonal MIN6 cells

et al. 2012

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Aims/hypothesis During the development of type 2 diabetes mellitus, beta cells are often exposed to a high glucose/ hyperlipidaemic environment, in which the levels of reactive oxygen species (ROS) are elevated. In turn, ROS can trigger an apoptotic response leading to beta cell death, by activating mitogen-activated protein kinase (MAPK) signalling cascades. Here we test the hypothesis that serine/threonine protein phosphatase 5 (PP5) acts to suppress proapoptotic c-Jun N-terminal kinase (JNK) signalling in beta cells. Methods Ppp5c−/− and Ppp5c +/+ mice were subjected to intraperitoneal glucose (IPGTT)

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Disruption of Serine/Threonine Protein Phosphatase 5 (PP5:PPP5c) in Mice Reveals a Novel Role for PP5 in the Regulation of Ultraviolet Light-induced Phosphorylation of Serine/Threonine Protein Kinase Chk1 (CHEK1)

Cited by 35 publications

References 48 publications

Decreased adipogenesis and adipose tissue in mice with inactivated protein phosphatase 5

Decreased adipogenesis and adipose tissue in mice with inactivated protein phosphatase 5

Knockdown of serine/threonine protein phosphatase 5 enhances gemcitabine sensitivity by promoting apoptosis in pancreatic cancer cells inï¿½vitro

Serine/threonine protein phosphatase 5 regulates glucose homeostasis in vivo and apoptosis signalling in mouse pancreatic islets and clonal MIN6 cells

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