The LIM-only protein FHL2 is a serum-inducible transcriptional coactivator of AP-1

Morlon, Aurore; Sassone–Corsi, Paolo

doi:10.1073/pnas.0735923100

Cited by 115 publications

(134 citation statements)

References 47 publications

(68 reference statements)

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“…Considering the data shown in Figure 4e, we wondered whether that this failure might reflect the fact that the pool of nuclear FHL2 was low in these growth conditions. Therefore, we repeated this experiment after exposure of U2OS cells to UV (30 J/m 2 ), a condition, which had been described to stimulate the nuclear translocation of FHL2 in exponentially growing fibroblasts (Morlon and Sassone-Corsi, 2003). Consistent with this report, we found that FHL2 nuclear accumulation was strongly stimulated 8 h after irradiation of U2OS cells (Figure 6b and c).…”

Section: Identification Of An Endogenous Fhl2-e4f1 Complex In Uv-irrasupporting

confidence: 85%

“…Consistent with this scenario, DRAL/FHL2 cellular localization seems to be both nuclear and non-nuclear (Scholl et al, 2000). Moreover, it undergoes a Rho-and Crm1-dependent nuclear accumulation in response to various gowth, morphogenic and apoptotic signals (Muller et al, 2002;Morlon and Sassone-Corsi, 2003). The physiological consequences of this DRAL/FHL2 nuclear accumulation remains unclear and might depend on the cellular context, on the signals that initiates shuttling and on its targets.…”

Section: Introductionmentioning

confidence: 76%

“…p120 E4F strongly stimulates the nuclear accumulation of downregulated in rhabdomyosarcoma Lim protein/FHL2 FHL2 was shown to localize in several cellular compartments and to undergo a continuous Crm1-dependent nuclear-cytoplasmic shuttling (Muller et al, 2002;Morlon and Sassone-Corsi, 2003). In contrast, E4F1 was reported to be exclusively nuclear.…”

Section: Resultsmentioning

confidence: 99%

“…Although expression of FHL2 is predominantly detected in the heart (Chan et al, 1998), it has also been observed in several extracardiac tissues at certain stages of development and in many (if not all) different cell lines in culture, including U2OS (Amaar et al, 2002) and fibroblastic cells used in this work. In these cell lines, FHL2 has been reported to localize in several cellular compartments, including focal adhesions (Scholl et al, 2000;Li et al, 2001;Gabriel et al, 2004), cytoplasm and nucleus (Scholl et al, 2000;Muller et al, 2002;Morlon and Sassone-Corsi, 2003). This cellular localization and/or expression of FHL2 in these cell lines have been shown to be highly regulated and might be an essential parameter in modulating different cellular functions.…”

Section: Lim-only Protein Fhl2 Is a Negative Regulator Of E4f1mentioning

confidence: 92%

“…Although the cellular functions of these FHL proteins remain largely unknown, recent studies suggest that they may act as transcriptional coregulators and mediators in signal transduction. Thus, upon ectopic expression in reporter assays, FHL2 behaves as a coactivator for several transcription factors, including AP-1 (Morlon and Sassone-Corsi, 2003), CREB (Fimia et al, 2000), androgen receptor (Muller et al, 2000), NF-kB (Stilo et al, 2002), WT1 (Du et al, 2002) and as a corepressor for the Promyelocytic leukemia zinc-finger protein (PLZF) (McLoughlin et al, 2002). Interestingly, DRAL/FHL2 was also described to directly associates with proteins involved in signal transduction, such as IGFBP-5 (Amaar et al, 2002), b-catenin (Martin et al, 2002;Wei et al, 2003;Labalette et al, 2004), a-and bintegrins (Wixler et al, 2000) and the map kinase erk2 (Purcell et al, 2004), suggesting that it might function as a molecular transmitter linking various signaling pathways to transcriptional regulation.…”

Section: Introductionmentioning

confidence: 99%

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The LIM-only protein FHL2 is a negative regulator of E4F1

et al. 2006

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The E1A-targeted transcription factor E4F1 is a key player in the control of mammalian embryonic and somatic cell proliferation and survival. Mouse embryos lacking E4F die at an early developmental stage, whereas enforced expression of E4F1 in various cell lines inhibits cell cycle progression. E4F1-antiproliferative effects have been shown to depend on its capacity to repress transcription and to interact with pRb and p53. Here we show that full-length E4F1 protein (p120 E4F1 ) but not its E1A-activated and truncated form (p50 E4F1 ), interacts directly in vitro and in vivo with the LIM-only protein FHL2, the product of the p53-responsive gene FHL2/ DRAL (downregulated in rhabdomyosarcoma Lim protein). This E4F1-FHL2 association occurs in the nuclear compartment and inhibits the capacity of E4F1 to block cell proliferation. Consistent with this effect, ectopic expression of FHL2 inhibits E4F1 repressive effects on transcription and correlates with a reduction of nuclear E4F1-p53 complexes. Overall, these results suggest that FHL2/DRAL is an inhibitor of E4F1 activity. Finally, we show that endogenous E4F1-FHL2 complexes form in U2OS cells upon UV-light-induced nuclear accumulation of FHL2.

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Section: Identification Of An Endogenous Fhl2-e4f1 Complex In Uv-irrasupporting

confidence: 85%

Section: Introductionmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Section: Lim-only Protein Fhl2 Is a Negative Regulator Of E4f1mentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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The LIM-only protein FHL2 is a negative regulator of E4F1

et al. 2006

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Screening and identification of a novel FHL2 mutation by whole exome sequencing in twins with familial Waldenström macroglobulinemia

Wan

Cheng

Liu

et al. 2021

Cancer

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BACKGROUND: Waldenström macroglobulinemia (WM) is a rare chronic B-cell lymphoma. Familial clustering of WM has been observed over the years. However, little is known about the contribution of inherited genetic variants to familial WM cases. METHODS: The authors performed whole exome sequencing (WES) of germline DNA samples from twins, one diagnosed with WM and the other diagnosed with immunoglobulin M monoclonal gammopathy of undetermined significance, and their healthy siblings. Bioinformatics analysis of public biological databases was used to identify the most relevant familial WM candidate from WES. Transcript expression and protein levels of the familial WM candidate were evaluated in the WM patient and 2 unaffected members of the kindred. RESULTS: Among the 10 shared candidate mutations in the twins, the authors identified a novel heterozygous germline mutation in four and a half LIM domains protein 2 (FHL2; c.G226A, p.V76M) as a familial WM-associated mutation. FHL2 appeared to be connected with reported signaling pathways and disease-driving genes such as IL6 and HCK in WM. In addition, the authors found reduced FHL2 messenger RNA and protein expression in peripheral blood samples from the patient with WM in comparison with the healthy siblings. CONCLUSIONS: Taken together, these findings indicate that an FHL2 g226a mutation may play an important role in familial WM, and they provide new screening possibilities for familial cases.

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Two‐Hybrid Fluorescence Cross‐Correlation Spectroscopy Detects Protein–Protein Interactions In Vivo

et al. 2005

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Fluorescence cross-correlation spectroscopy (FCCS) uses the correlated motion of two distinct fluorophores to detect their interaction. Whereas FCCS has been used with chemically or genetically labeled interaction partners in vitro, FCCS has never been demonstrated in vivo between two autofluorescent proteins. At least one reaction partner was always chemically labeled. Fos and Jun, two components of the AP-1 transcription factor, are known to exert their function as a dimer and can therefore serve as a reference for dimer formation. Expressing fusion proteins between Fos and the enhanced green fluorescent protein (EGFP), as well as Jun and the monomeric red fluorescent protein 1 (mRFP1) in HeLa cells, we show here, for the first time, in vivo FCCS detection of protein-protein interactions. The mobility of the dimerized species is slow, indicating that DNA-binding might stabilize dimerization. The technique has rich potential applications for the rapid screening of protein-protein interactions in vivo, which are able to clarify events during the whole life of cells.

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The LIM-only protein FHL2 is a serum-inducible transcriptional coactivator of AP-1

Cited by 115 publications

References 47 publications

The LIM-only protein FHL2 is a negative regulator of E4F1

The LIM-only protein FHL2 is a negative regulator of E4F1

Screening and identification of a novel FHL2 mutation by whole exome sequencing in twins with familial Waldenström macroglobulinemia

Two‐Hybrid Fluorescence Cross‐Correlation Spectroscopy Detects Protein–Protein Interactions In Vivo

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