LKB1 induces apical trafficking of Silnoon, a monocarboxylate transporter, in Drosophila melanogaster

Silnoon (Sln) is a monocarboxylate transporter (MCT) that mediates active transport of metabolic monocarboxylates such as butyrate and lactate. Here, we identify Sln as a novel LKB1-interacting protein using Drosophila melanogaster genetic modifier screening. Sln expression does not affect cell cycle progression or cell size but specifically enhances LKB1-dependent apoptosis and tissue size reduction. Conversely, down-regulation of Sln suppresses LKB1-dependent apoptosis, implicating Sln as a downstream mediator of LKB1. The kinase activity of LKB1 induces apical trafficking of Sln in polarized cells, and LKB1-dependent Sln trafficking is crucial for triggering apoptosis induced by extracellular butyrate. Given that LKB1 functions to control both epithelial polarity and cell death, we propose Sln is an important downstream target of LKB1.

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Pericyte contractility controls endothelial cell cycle progression and sprouting: insights into angiogenic switch mechanics

AJP Cell Physiology ◽

10.1152/ajpcell.00185.2014 ◽

2014 ◽

Vol 307 (9) ◽

pp. C878-C892 ◽

Cited By ~ 21

Author(s):

Jennifer T. Durham ◽

Howard K. Surks ◽

Brian M. Dulmovits ◽

Ira M. Herman

Keyword(s):

Cell Cycle Progression ◽

Network Formation ◽

Rho Gtpase ◽

Three Dimensional ◽

Rho Kinase ◽

Leading Edge ◽

Fold Increase ◽

Cycle Progression ◽

Interacting Protein ◽

Angiogenic Switch

Microvascular stability and regulation of capillary tonus are regulated by pericytes and their interactions with endothelial cells (EC). While the RhoA/Rho kinase (ROCK) pathway has been implicated in modulation of pericyte contractility, in part via regulation of the myosin light chain phosphatase (MLCP), the mechanisms linking Rho GTPase activity with actomyosin-based contraction and the cytoskeleton are equivocal. Recently, the myosin phosphatase-RhoA-interacting protein (MRIP) was shown to mediate the RhoA/ROCK-directed MLCP inactivation in vascular smooth muscle. Here we report that MRIP directly interacts with the β-actin-specific capping protein βcap73. Furthermore, manipulation of MRIP expression influences pericyte contractility, with MRIP silencing inducing cytoskeletal remodeling and cellular hypertrophy. MRIP knockdown induces a repositioning of βcap73 from the leading edge to stress fibers; thus MRIP-silenced pericytes increase F-actin-driven cell spreading twofold. These hypertrophied and cytoskeleton-enriched pericytes demonstrate a 2.2-fold increase in contractility upon MRIP knockdown when cells are plated on a deformable substrate. In turn, silencing pericyte MRIP significantly affects EC cycle progression and angiogenic activation. When MRIP-silenced pericytes are cocultured with capillary EC, there is a 2.0-fold increase in EC cycle entry. Furthermore, in three-dimensional models of injury and repair, silencing pericyte MRIP results in a 1.6-fold elevation of total tube area due to EC network formation and increased angiogenic sprouting. The pivotal role of MRIP expression in governing pericyte contractile phenotype and endothelial growth should lend important new insights into how chemomechanical signaling pathways control the “angiogenic switch” and pathological angiogenic induction.

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Voltage-Gated Potassium Channels as Regulators of Cell Death

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.611853 ◽

2020 ◽

Vol 8 ◽

Author(s):

Magdalena Bachmann ◽

Weiwei Li ◽

Michael J. Edwards ◽

Syed A. Ahmad ◽

Sameer Patel ◽

...

Keyword(s):

Ion Channels ◽

Cell Cycle Progression ◽

Current Knowledge ◽

Ion Homeostasis ◽

Cycle Progression ◽

Voltage Gated ◽

Proliferation And Apoptosis ◽

Affect Cell Cycle Progression ◽

Voltage Gated Channels ◽

Intracellular Potassium Concentration

Ion channels allow the flux of specific ions across biological membranes, thereby determining ion homeostasis within the cells. Voltage-gated potassium-selective ion channels crucially contribute to the setting of the plasma membrane potential, to volume regulation and to the physiologically relevant modulation of intracellular potassium concentration. In turn, these factors affect cell cycle progression, proliferation and apoptosis. The present review summarizes our current knowledge about the involvement of various voltage-gated channels of the Kv family in the above processes and discusses the possibility of their pharmacological targeting in the context of cancer with special emphasis on Kv1.1, Kv1.3, Kv1.5, Kv2.1, Kv10.1, and Kv11.1.

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Monocytes affect cell-cycle progression but not baseline frequency of sister chromatid exchanges of pig lymphocytes

Environmental and Molecular Mutagenesis ◽

10.1002/(sici)1098-2280(1999)33:1<86::aid-em10>3.0.co;2-# ◽

1999 ◽

Vol 33 (1) ◽

pp. 86-90

Author(s):

Sonia Soloneski ◽

Carlos F. Garcia ◽

Miguel A. Reigosa ◽

Marcelo L. Larramendy

Keyword(s):

Cell Cycle ◽

Sister Chromatid ◽

Cell Cycle Progression ◽

Sister Chromatid Exchanges ◽

Cycle Progression ◽

Affect Cell Cycle Progression ◽

Baseline Frequency ◽

Chromatid Exchanges

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DNA Damage during G2 Phase Does Not Affect Cell Cycle Progression of the Green Alga Scenedesmus quadricauda

PLoS ONE ◽

10.1371/journal.pone.0019626 ◽

2011 ◽

Vol 6 (5) ◽

pp. e19626 ◽

Cited By ~ 10

Author(s):

Monika Hlavová ◽

Mária Čížková ◽

Milada Vítová ◽

Kateřina Bišová ◽

Vilém Zachleder

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Green Alga ◽

Cell Cycle Progression ◽

Scenedesmus Quadricauda ◽

Cycle Progression ◽

Affect Cell Cycle Progression ◽

G2 Phase ◽

Alga Scenedesmus Quadricauda

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MLL-AF4 Down-Regulates CDKN1B (P27) Independent of Cell Cycle Progression.

Blood ◽

10.1182/blood.v104.11.2563.2563 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2563-2563

Author(s):

Zhenbiao Xia ◽

Relja Popovic ◽

Tara Lorenz ◽

Donna Santillan ◽

Frank Erfurth ◽

...

Keyword(s):

Cell Cycle ◽

Cell Growth ◽

Cell Line ◽

Cell Cycle Progression ◽

Target Genes ◽

Leukemia Cell ◽

Leukemia Cell Line ◽

Luciferase Reporter ◽

Cycle Progression ◽

Downstream Target

Abstract The MLL gene, involved in many chromosomal translocations associated with acute myeloid and lymphoid leukemia, has more than forty known partner genes with which it is able to form in- frame fusions. MLL fusion genes transform hematopoietic cells in vitro, and cause leukemia in mouse models. However, the mechanism is still not clear. Characterizing important downstream target genes may provide rational therapeutic strategies for the treatment of MLL-associated leukemia. We explored potential downstream target genes of the most prevalent MLL fusion protein, MLL-AF4, which is primarily associated with pro-B ALL and is involved in the majority of infant leukemia. To this end, we developed an inducible MLL-AF4 fusion cell line. Overexpression of MLL-AF4 does not lead to increased proliferation in this cell line, but rather, cell growth is slowed compared to similar cell lines inducibly expressing truncated MLL. To try to understand the reason for slower cell growth, we assayed for expression of several CDK inhibitors. We found that in the MLL-AF4 induced cell line, the amount of CDKN1B (cyclin-dependent kinase inhibitor P27) was dramatically decreased both at the RNA and protein levels, in contrast, the levels of CDKN1A (P21) and CDKN2A (P16) were unchanged. Interestingly, we did not observe an increased percentage of cells in S phase of the cell cycle. To explore whether CDKN1B might be a direct target of MLL-AF4, we employed chromatin immunoprecipitation (ChIP) assays and luciferase reporter gene assays. We observed that MLL-AF4 binds to the CDKN1B promoter in vivo and represses CDKN1B promoter activity. Further, we confirmed CDKN1B promoter binding by ChIP assays in the MLL-AF4 leukemia cell line MV4-11. Our results suggest that the CDKN1B may be a downstream target of MLL-AF4, and that MLL-AF4 inhibits CDKN1B expression independent of cell cycle progression.

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Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation

Blood ◽

10.1182/blood-2009-07-235093 ◽

2010 ◽

Vol 115 (23) ◽

pp. 4853-4861 ◽

Cited By ~ 30

Author(s):

Shilpa M. Hattangadi ◽

Karly A. Burke ◽

Harvey F. Lodish

Keyword(s):

Cell Cycle Progression ◽

Fetal Liver ◽

Erythroid Differentiation ◽

Erythroid Cell ◽

Cycle Progression ◽

Interacting Protein ◽

Primary Mouse ◽

Proliferation And Apoptosis ◽

Hemoglobin Biosynthesis ◽

Terminal Erythroid Differentiation

Abstract Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic development because Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis, whereas the single knockouts do not. These serine-threonine kinases phosphorylate and consequently modify the functions of several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alone plays a significant role in terminal fetal liver erythroid differentiation. Hipk1 and Hipk2 are highly induced during primary mouse fetal liver erythropoiesis. Specific knockdown of Hipk2 inhibits terminal erythroid cell proliferation (explained in part by impaired cell-cycle progression as well as increased apoptosis) and terminal enucleation as well as the accumulation of hemoglobin. Hipk2 knockdown also reduces the transcription of many genes involved in proliferation and apoptosis as well as important, erythroid-specific genes involved in hemoglobin biosynthesis, such as α-globin and mitoferrin 1, demonstrating that Hipk2 plays an important role in some but not all aspects of normal terminal erythroid differentiation.

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