pp32 Reduction Induces Differentiation of TSU-Pr1 Cells

Brody, Jonathan R.; Kadkol, Shrihari S.; Hauer, M.; Rajaii, Fatemeh; Lee, Jessica; Pasternack, Gary R.

doi:10.1016/s0002-9440(10)63117-3

Cited by 27 publications

(27 citation statements)

References 26 publications

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“…49 Although these data seem contradictory to our findings the two data sets are difficult to compare because the authors did not assess the effect of SET overexpression in TSU-Pr1 cells. In addition, the effects of SET might be different in different cell types.…”

Section: Set Induces Dendritic Cell-like Differentiation Of U937 Cellscontrasting

confidence: 92%

SET-induced calcium signaling and MAPK/ERK pathway activation mediate dendritic cell-like differentiation of U937 cells

Kandilci

Grosveld

2005

Leukemia

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Human SET, a target of chromosomal translocation in human leukemia encodes a highly conserved, ubiquitously expressed, nuclear phosphoprotein. SET mediates many functions including chromatin remodeling, transcription, apoptosis and cell cycle control. We report that overexpression of SET directs differentiation of the human promonocytic cell line U937 along the dendritic cell (DC) pathway, as cells display typical morphologic changes associated with DC fate and express the DC surface markers CD11b and CD86. Differentiation occurs via a calcium-dependent mechanism involving the CaMKII and MAPK/ERK pathways. Similar responses are elicited by interferon-c (IFN-c) treatment with the distinction that IFN-c signaling activates the DNA-binding activity of STAT1 whereas SET overexpression does not. In addition, unlike IFN-c signaling, SET generated stress-induced p38/MAPK activity. Interestingly, IFN-c treatment transiently upregulated endogenous SET in a dose-dependent manner. These results suggest that SET is part of both IFN-c-mediated and stress-mediated cellular responses and that SET induces cell differentiation via calcium and MAPK/ ERK pathways.

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Section: Set Induces Dendritic Cell-like Differentiation Of U937 Cellscontrasting

confidence: 92%

SET-induced calcium signaling and MAPK/ERK pathway activation mediate dendritic cell-like differentiation of U937 cells

Kandilci

Grosveld

2005

Leukemia

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“…However, in some cancers, pp32 is highly expressed, such as highly malignant prostatic adenocarcinomas. 27,28 A fairly recent study has shown hyperphosphorylated Rb, the retinoblastoma gene product, associates with pp32. 29 Rb is an important tumor suppressor and cell cycle regulator, that controls the G1/S transition, whose active form is a hypophosphorylated state.…”

Section: Discussionmentioning

confidence: 99%

Tumor suppressor pp32 represses cell growth through inhibition of transcription by blocking acetylation and phosphorylation of histone H3 and initiating its proapoptotic activity

Fan

Zhang

2005

Cell Death Differ

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pp32 belongs to a family of leucine-rich acidic nuclear proteins, which play important roles in many cellular processes including regulation of chromatin remodeling, transcription, RNA transport, transformation and apoptosis. pp32 is described as a new tumor suppressor. It is unknown as to how pp32 works in tumor suppression. We found that overexpression of pp32 in human Jurkat T cells inhibits cell growth, and silenced pp32 promotes growth. We first showed that hyperacetylation and hyperphosphorylation of histone H3 are required for T-cell activation. Phosphorylation of histone H3 precedes acetylation during T-cell activation. pp32 specifically binds to histone H3 and blocks its acetylation and phosphorylation. pp32 directly initiates caspase activity and also promotes granzyme A-mediated caspase-independent cell death. Taken together, pp32 plays a repressive role by inhibiting transcription and triggering apoptosis.

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“…It accelerates caspase activation by stimulating the apoptosome, but the in vivo significance of this is unclear. In contradistinction to its pro-apoptotic and transformation inhibition functions, pp32 is highly expressed in cancer (37). In fact, pp32 is more highly expressed in highly malignant prostatic adenocarcinomas with Gleason scores of Ն5 than in clinically indolent tumors with Gleason scores of Ͻ5 (38).…”

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Phosphorylated Retinoblastoma Protein Complexes with pp32 and Inhibits pp32-mediated Apoptosis

Adegbola¹,

Pasternack

2005

Journal of Biological Chemistry

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The retinoblastoma gene product (Rb) is a tumor suppressor that affects apoptosis paradoxically. Most sporadic cancers inactivate Rb by preferentially targeting the pathway that regulates Rb phosphorylation, resulting in resistance to apoptosis; this contrasts with Rb inactivation by mutation, which is associated with high rates of apoptosis. How phosphorylated Rb protects cells from apoptosis is not well understood, but there is evidence that Rb may sequester a pro-apoptotic nuclear factor. pp32 (ANP32A) is a pro-apoptotic nuclear phosphoprotein, the expression of which is commonly increased in cancer. We report that hyperphosphorylated Rb interacts with pp32 but not with the closely related proteins pp32r1 and pp32r2. We further demonstrate that pp32-Rb interaction inhibits the apoptotic activity of pp32 and stimulates proliferation. These results suggest a mechanism whereby cancer cells gain both a proliferative and survival advantage when Rb is inactivated by hyperphosphorylation.The retinoblastoma protein (Rb) 1 is a nuclear phosphoprotein that regulates proliferation, differentiation, and apoptosis. As a tumor suppressor, Rb inhibits proliferation by repressing E2F1-mediated transcription when hypophosphorylated. Hyperphosphorylation of Rb relieves E2F1 repression and allows cell cycle progression to occur (1). The importance of Rb is underscored by the fact that Rb function is disrupted in virtually all human cancers (2). Paradoxically and inconsistent with its role as a tumor suppressor, hyperphosphorylated wild-type Rb inhibits apoptosis in both cell culture and animal models (3)(4)(5)(6)(7)(8)(9)(10). Because Rb inactivation is pivotal for carcinogenesis, this poses the problem of how cancer cells escape apoptosis when Rb function is disrupted.Inherited cancers and cells in which Rb is inactivated by mutation have increased rates of both proliferation and apoptosis (11). Most sporadic cancers preferentially inactivate Rb by hyperphosphorylation, which may occur through mutation of cyclin D, cdk4, or p16. Such cancers are generally slow growing and resistant to apoptosis induced by chemotherapy or radiation (12). It is possible that in these cancers the tumor suppressor function of Rb is inhibited, whereas the anti-apoptotic function remains intact (13). Inactivation by hyperphosphorylation might promote proliferation by increasing free E2F1, as well as inhibit apoptosis by retaining the anti-apoptotic function of Rb. This is consistent with evidence suggesting that it is the hyperphosphorylated form of Rb rather than Rb per se that protects cells from apoptosis (14). The induction of apoptosis in various cell lines is accompanied by a shift in Rb from the hyperphosphorylated to the hypophosphorylated form (15,16). Rb dephosphorylation, which has been shown to be required for apoptosis, occurs in the early stage of apoptosis (17,18). Inhibition of Rb dephosphorylation prevents apoptosis, whereas induction of dephosphorylation leads to apoptosis (19). In DBA/2 mice, increased levels of hyperphosphoryla...

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pp32 Reduction Induces Differentiation of TSU-Pr1 Cells

Cited by 27 publications

References 26 publications

SET-induced calcium signaling and MAPK/ERK pathway activation mediate dendritic cell-like differentiation of U937 cells

SET-induced calcium signaling and MAPK/ERK pathway activation mediate dendritic cell-like differentiation of U937 cells

Tumor suppressor pp32 represses cell growth through inhibition of transcription by blocking acetylation and phosphorylation of histone H3 and initiating its proapoptotic activity

Phosphorylated Retinoblastoma Protein Complexes with pp32 and Inhibits pp32-mediated Apoptosis

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