Role of Promyelocytic Leukemia Zinc Finger (PLZF) in Cell Proliferation and Cyclin-dependent Kinase Inhibitor 1A (p21WAF/CDKN1A) Gene Repression

Choi, Won‐Il; Kim, Min Young; Jeon, Bu Nam; Koh, Dong In; Yun, Chae Ok; Li, Yan; Lee, Choong Eun; Oh, Jiyoung; Kim, Kunhong; Hur, Man‐Wook

doi:10.1074/jbc.m113.538751

Cited by 40 publications

(33 citation statements)

References 36 publications

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“…Previous investigations have demonstrated a pleiotropic regulatory role for PLZF in a myriad of developmental programs and physiological responses, from hind-limb skeletal patterning [ 11 ] to spermatogonial stem-cell maintenance [ 18 , 19 ]. Due to its role in limiting cell-cycle progression and cellular proliferation [ 20 , 21 ], PLZF is known to act as a tumor suppressor in a broad spectrum of malignancies [ 22 – 26 ]. At the transcriptional level, PLZF is known primarily as a repressor; reviewed in [ 16 ]; however, an increasing number of studies describe PLZF as an activator of transcription [ 27 – 31 ].…”

Section: Discussionmentioning

confidence: 99%

The Promyelocytic Leukemia Zinc Finger Transcription Factor Is Critical for Human Endometrial Stromal Cell Decidualization

et al. 2016

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Progesterone, via the progesterone receptor (PGR), is essential for endometrial stromal cell decidualization, a cellular transformation event in which stromal fibroblasts differentiate into decidual cells. Uterine decidualization supports embryo implantation and placentation as well as subsequent events, which together ensure a successful pregnancy. Accordingly, impaired decidualization results not only in implantation failure or early fetal miscarriage, but also may lead to potential adverse outcomes in all three pregnancy trimesters. Transcriptional reprogramming on a genome-wide scale underlies progesterone dependent decidualization of the human endometrial stromal cell (hESC). However, identification of the functionally essential signals encoded by these global transcriptional changes remains incomplete. Importantly, this knowledge-gap undercuts future efforts to improve diagnosis and treatment of implantation failure based on a dysfunctional endometrium. By integrating genome-wide datasets derived from decidualization of hESCs in culture, we reveal that the promyelocytic leukemia zinc finger (PLZF) transcription factor is rapidly induced by progesterone and that this induction is indispensable for progesterone-dependent decidualization. Chromatin immunoprecipitation followed by next generation sequencing (ChIP-Seq) identified at least ten progesterone response elements within the PLZF gene, indicating that PLZF may act as a direct target of PGR signaling. The spatiotemporal expression profile for PLZF in both the human and mouse endometrium offers further support for stromal PLZF as a mediator of the progesterone decidual signal. To identify functional targets of PLZF, integration of PLZF ChIP-Seq and RNA Pol II RNA-Seq datasets revealed that the early growth response 1 (EGR1) transcription factor is a PLZF target for which its level of expression must be reduced to enable progesterone dependent hESC decidualization. Apart from furnishing essential insights into the molecular mechanisms by which progesterone drives hESC decidualization, our findings provide a new conceptual framework that could lead to new avenues for diagnosis and/or treatment of adverse reproductive outcomes associated with a dysfunctional uterus.

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Section: Discussionmentioning

confidence: 99%

The Promyelocytic Leukemia Zinc Finger Transcription Factor Is Critical for Human Endometrial Stromal Cell Decidualization

et al. 2016

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“…Although overexpression of PLZF leads to a block of cell cycle progression in a myelomonocytic cell line (U937T) (38), it was recently described that PLZF expression may stimulate proliferation in NIH3T3 cells by repressing expression of Cdkn1a (p21), a negative regulator of cell cycle progression (39), however, we did not find increased Cdkn1a levels in PLZF-deficient Vγ6 + γδT-cells ( data not shown ), indicating that PLZF is required for other mechanisms of cell cycle control in Vγ6 + γδT-cells.…”

Section: Discussionmentioning

confidence: 99%

PLZF Controls the Development of Fetal-Derived IL-17+Vγ6+ γδ T Cells

Cao

Zhang

et al. 2015

The Journal of Immunology

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Expression of promyelocytic leukemia zinc finger (PLZF) protein directs the effector differentiation of invariant NKT (iNKT) cells and IL-4+γδNKT cells. We show here that PLZF is also required for the development and function of IL-17+γδT-cells. We observed that PLZF is expressed in fetal-derived invariant Vγ5+ and Vγ6+γδT-cells, which secrete IFN-γ and IL-17 respectively. PLZF-deficiency specifically affected the effector differentiation of Vγ6+ cells, leading to reduced numbers of mature CD27−CD44+ phenotype capable of secreting IL-17. Although PLZF was not required for Vγ5+γδT-cells to develop, when these cells were re-programmed into IL-17-secreting cells in SkinT-mutant mice, they required PLZF for their effector maturation, similarly to Vγ6+γδT-cells. The impaired effector differentiation of PLZF-deficient Vγ6+ γδT-cells was not due to increased apoptosis and it was related to reduced proliferation of immature CD27+CD44− Vγ6+γδT-cells, which was required for their differentiation into mature CD27−CD44+ IL-17-secreting cells. Thus, this work identifies that PLZF function is not restricted to NKT or IL-4+ T-cells cells but it also controls the development of IL-17+ γδT-cells.

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“…Overexpression of p21 may also inhibit CDK1 and prevent G2/M transition. Moreover, p21 has also been demonstrated to inhibit the kinase activity of cyclin A/CDK2, thereby inhibiting the cell cycle through S phase arrest (28,29). Therefore, numerus studies have shown that p21 plays a central role in carcinogenesis-associated cell cycle regulation and DNA repair (30).…”

Section: Discussionmentioning

confidence: 99%

Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade

Huang

Chen

et al. 2020

Int. J. Med. Sci.

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Background: Adenine exhibits potential anticancer activity against several types of malignancies. However, whether adenine has anticancer effects on hepatocellular carcinoma (HCC) cells is incompletely explored. Methods: Human HCC cell lines HepG2 and SK-Hep-1 (p53-wild type) and Hep3B (p53-deficient) were used as cell model. Cell growth and cell cycle distribution were determined using MTT assay and flow cytometric analysis, respectively. Protein expression and phosphorylation were assessed by Western blot. Involvement of AMP-activated protein kinase (AMPK) was evaluated using specific inhibitor and small inhibitory RNA (siRNA). Results: Adenine treatments (0.5 -2 mM) clearly decreased the cell growth of Hep G2 and SK-Hep-1 cells to 72.5 ± 3.4% and 71.3 ± 4.6% of control, respectively. In parallel, adenine also induced sub-G1 and S phase accumulation in both HCC cells. However, adenine did not affect the cell growth and cell cycle distribution of Hep3B cell. Western blot analysis showed that adenine reduced expression of cyclin A/D1 and cyclin-dependent kinase (CDK)2 and upregulated p53, p21, Bax, PUMA, and NOXA in HepG2 cell. Moreover, adenine induced AMPK activation that was involved in the p53-associated apoptotic cascade in HepG2 cells. Inhibition of AMPK activation or knockdown of AMPK restored the decreased cell growth of HepG2 and SK-Hep-1 cells in response to adenine. Conclusions: These findings reveal that adenine reduces the cell growth of HepG2 and SK-Hep-1 but not Hep3B cells, attributing to the AMPK/p53-mediated S phase arrest and apoptosis. It suggests that adenine has anticancer potential against p53-wild type HCC cells and may be beneficial as an adjuvant for HCC treatment.

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Role of Promyelocytic Leukemia Zinc Finger (PLZF) in Cell Proliferation and Cyclin-dependent Kinase Inhibitor 1A (p21WAF/CDKN1A) Gene Repression

Cited by 40 publications

References 36 publications

The Promyelocytic Leukemia Zinc Finger Transcription Factor Is Critical for Human Endometrial Stromal Cell Decidualization

The Promyelocytic Leukemia Zinc Finger Transcription Factor Is Critical for Human Endometrial Stromal Cell Decidualization

PLZF Controls the Development of Fetal-Derived IL-17+Vγ6+ γδ T Cells

Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade

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