FHL2 interacts with and acts as a functional repressor of Id2 in human neuroblastoma cells

Han, Weidong; Wu, Zhiqiang; Zhao, Yali; Si, Yanna; Fu, Xiaobing

doi:10.1007/s11670-009-0081-0

Cited by 4 publications

(4 citation statements)

References 44 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on its specific domain structure, FHL2 mediates multiple cellular activities, including gene transcription, signal transduction, apoptosis, and cell proliferation . Some reports have shown that the effect of FHL2 on cells is dependent on regulation of the cytoskeleton, transcription factors, or nuclear receptors . We also found that FHL2 is dependent on cytoskeletal regulation in MCs by colocalizing with F‐actin.…”

Section: Introductionsupporting

confidence: 55%

FHL2-driven molecular network mediated Septin2 knockdown inducing apoptosis in mesangial cell

et al. 2014

View full text Add to dashboard Cite

The apoptosis of mesangial cells (MCs) plays a critical role in the pathological progress of MesPGN. Septin2, a filamentous GTPase, is implicated in the apoptotic progress of MCs in the rat MesPGN model. However, the molecular mechanism of SEPT2 in MCs apoptosis is not clear. Here, we present the FHL2-driven molecular network as the main mechanism of SEPT2-mediated rat primary MCs apoptosis. First, we proved that the expression of FHL2 and Septin2 were closely related with MCs apoptosis in anti-Thy1 nephritis model. Then, it was found that FHL2 was a new interaction protein of Septin2 and Septin2 knockdown could induce MC apoptosis by FHL2-mediatied signal pathways including p-ERK1 and p-AKT. We applied label-Free quantitative proteomics to identify the mechanism of Septin2/FHL2-regulated apoptosis. Bioinformatics analysis revealed that FHL2-driven molecular network composed of biological functions including glycolysis, oxidative stress, ribonucleotide metabolism, actin cytoskeleton regulation, and signaling pathway, was the main mechanism of SETP2-mediated apoptosis. Furthermore, we showed that the effect of Septin2 knockdown on MC apoptosis could be alleviated by the overexpression of FHL2. Overall, this study illustrated the FHL2-driven molecular network controlling SEPT2-mediated apoptosis in MCs and their potential roles in mesangial proliferative nephritis.

show abstract

Section: Introductionsupporting

confidence: 55%

FHL2-driven molecular network mediated Septin2 knockdown inducing apoptosis in mesangial cell

et al. 2014

View full text Add to dashboard Cite

show abstract

“…It is likely that other regulatory factors cooperate with Id2 to direct the differentiation of mesodermal progenitors into distinct connective tissues. The functional repressor of Id2, FHL2 gene, might be a good candidate for this function because it is upregulated in micromass cultures treated with NOGGIN (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Ligand- and Stage-Dependent Divergent Functions of BMP Signaling in the Differentiation of Embryonic Skeletogenic Progenitors In Vitro

Lorda‐Diez

Montero

Choe

et al. 2013

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Bone morphogenetic proteins (BMPs) are key molecules in the differentiation of skeletal tissues. We have investigated whether differentiation of limb embryonic mesodermal progenitors into different connective tissue lineages depends on specific stimulation of distinct BMP ligands or on the differential response of target cells to a common BMP stimulus. We show that Bmp2,4,5,7 and Gdf5 exhibit differential expression domains during the formation of tendons, cartilages, and joint tissues in digit development, but their respective effects on digit progenitors cell cultures cannot sustain the divergent differentiation of these cells into tendons, joints, and cartilage. However, the influence of BMPs differs based on the culture length. Early cultures respond to any of the BMPs by inducing chondrogenic factors and inhibiting fibrogenic and osteogenic markers. Later, a second phase of the culture occurs when BMPs attenuate their prochondrogenic influence and promote the fibrogenic marker Scleraxis. At advanced culture stages, BMPs inhibit prochondrogenic and profibrogenic markers and promote osteogenic markers. The switch from the prochondrogenic to the profibrogenic response appears critically dependent on the basal expression of Noggin. Thus, the differential regulation of Scleraxis at these stages was abrogated by treatments with a BMP-analogous compound (AB204) that escapes NOGGIN antagonism. Gene regulation experiments in absence of protein synthesis during the first period of culture indicate that BMPs activate at the same time master chondrogenic and fibrogenic genes together with cofactors responsible for driving the signaling cascade toward chondrogenesis or fibrogenesis. Gene-silencing experiments indicate that Id2 is one of the factors limiting the profibrogenic influence of BMPs. We propose that connective tissues are dynamic structures composed of cartilage, fibrous tissue, and bone that form in successive steps from the differentiation of common progenitors. This sequential differentiation is regulated by BMPs through a process that is dependent on the basal expression of BMP cofactors or signaling modulators.

show abstract

“…FHL2 is involved in many processes, including cell cycle regulation (31,41), apoptosis (55,60), differentiation (21,32,40,63), extracellular matrix assembly (48), bone formation (20), and wound healing (28,65). Although the highest expression of FHL2 occurs in the heart, knockout mice are viable and display no overt cardiac phenotype under basal conditions (5,30).…”

mentioning

confidence: 99%

FHL2 Binds Calcineurin and Represses Pathological Cardiac Growth

Hojayev

Rothermel²,

Gillette³

et al. 2012

Molecular and Cellular Biology

View full text Add to dashboard Cite

Stress-induced hypertrophic growth of the heart predisposes the heart to arrhythmia, contractile dysfunction, and clinical heart failure. FHL2 (four-and-a-half LIM domain protein 2) is expressed predominantly in the heart, and inactivation of the gene coding for FHL2 leads to exaggerated responsiveness to adrenergic stress. Activation of calcineurin occurs downstream of ␤-adrenergic signaling and is required for isoproterenol-induced myocardial hypertrophy. Based on these facts, we hypothesized that FHL2 suppresses stress-induced activation of calcineurin. FHL2 is upregulated in mouse hearts exposed to isoproterenol, a ␤-adrenergic agonist, and isoproterenol-induced increases in the NFAT target genes RCAN1.4 and BNP were amplified significantly in FHL2 knockout (FHL2 ؊/؊ ) mice compared with levels in wild-type (WT) mice. To determine whether the effect of FHL2 on NFAT target gene transcript levels occurred at the level of transcription, HEK 293 cells and neonatal rat ventricular myocytes (NRVMs) were transfected with a luciferase reporter construct harboring the NFAT-dependent promoters of either RCAN1 or interleukin 2 (IL-2). Consistent with the in vivo data, small interfering RNA (siRNA) knockdown of FHL2 led to increased activation of these promoters by constitutively active calcineurin or the calcium ionophore ionomycin. Importantly, activation of the RCAN1 promoter by ionomycin, in control and FHL2 knockdown cells, was abolished by the calcineurin inhibitor cyclosporine, confirming the calcineurin dependence of the response. Overexpression of FHL2 inhibited activation of both NFAT reporter constructs. Furthermore, NRVMs overexpressing FHL2 exhibited reduced hypertrophic growth in response to constitutively active calcineurin, as measured by cell cross-sectional area and fetal gene expression. Finally, immunostaining in isolated adult cardiomyocytes revealed colocalization of FHL2 and calcineurin predominantly at the sarcomere and activation of calcineurin by endothelin-1-facilitated interaction between FHL2 and calcineurin. FHL2 is an endogenous, agonist-dependent suppressor of calcineurin. E pidemiological evidence links left ventricular (LV) hypertrophy with adverse cardiovascular events, including heart failure and death (1,13,35,36). Consistent with this, therapies that improve clinical outcomes are often associated with regression of ventricular hypertrophy (11,19,46). However, whereas significant strides have been made in elucidating the molecular circuitry governing pathological cardiac remodeling (23), few therapies in clinical use target cell growth mechanisms directly.Hypertrophic growth of the heart in response to a variety of pathological stresses is an initially adaptive response that, left unchecked, often progresses to heart failure (25). In many instances, the intracellular protein phosphatase calcineurin is a major mediator of stress-induced cardiac hypertrophy. Upon activation, calcineurin dephosphorylates NFAT (nuclear factor of activated T cells), which, in turn, translocates into the n...

show abstract

FHL2 interacts with and acts as a functional repressor of Id2 in human neuroblastoma cells

Cited by 4 publications

References 44 publications

FHL2-driven molecular network mediated Septin2 knockdown inducing apoptosis in mesangial cell

FHL2-driven molecular network mediated Septin2 knockdown inducing apoptosis in mesangial cell

Ligand- and Stage-Dependent Divergent Functions of BMP Signaling in the Differentiation of Embryonic Skeletogenic Progenitors In Vitro

FHL2 Binds Calcineurin and Represses Pathological Cardiac Growth

Contact Info

Product

Resources

About