TRIM45 negatively regulates NF-κB-mediated transcription and suppresses cell proliferation

Shibata, Mio; Satô, Tomonobu; Nukiwa, Ryota; Ariga, Tadashi; Hatakeyama, Susumi

doi:10.1016/j.bbrc.2012.05.090

Cited by 42 publications

(27 citation statements)

References 38 publications

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“…DENND2D was shown to be down-regulated in non-small cell lung cancer and might act as a tumor-suppressor gene [49], and suppressed expression was observed for patients with relapses in our study. TRIM45 suppresses cell proliferation as a repressor of the NF-κB signal pathway [50], and down-regulation was also observed in the relapsing Han Chinese patients in this study. SCRN1 was reported in Perou’s breast cancer intrinsic genes list and was speculated to be a prognostic marker in colorectal cancer [2-4,51].…”

Section: Discussionsupporting

confidence: 63%

Concurrent Gene Signatures for Han Chinese Breast Cancers

Huang¹,

Lien

et al. 2013

PLoS ONE

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The interplay between copy number variation (CNV) and differential gene expression may be able to shed light on molecular process underlying breast cancer and lead to the discovery of cancer-related genes. In the current study, genes concurrently identified in array comparative genomic hybridization (CGH) and gene expression microarrays were used to derive gene signatures for Han Chinese breast cancers.We performed 23 array CGHs and 81 gene expression microarrays in breast cancer samples from Taiwanese women. Genes with coherent patterns of both CNV and differential gene expression were identified from the 21 samples assayed using both platforms. We used these genes to derive signatures associated with clinical ER and HER2 status and disease-free survival.Distributions of signature genes were strongly associated with chromosomal location: chromosome 16 for ER and 17 for HER2. A breast cancer risk predictive model was built based on the first supervised principal component from 16 genes (RCAN3, MCOLN2, DENND2D, RWDD3, ZMYM6, CAPZA1, GPR18, WARS2, TRIM45, SCRN1, CSNK1E, HBXIP, CSDE1, MRPL20, IKZF1, and COL20A1), and distinct survival patterns were observed between the high- and low-risk groups from the combined dataset of 408 microarrays. The risk score was significantly higher in breast cancer patients with recurrence, metastasis, or mortality than in relapse-free individuals (0.241 versus 0, P<0.001). The concurrent gene risk predictive model remained discriminative across distinct clinical ER and HER2 statuses in subgroup analysis. Prognostic comparisons with published gene expression signatures showed a better discerning ability of concurrent genes, many of which were rarely identifiable if expression data were pre-selected by phenotype correlations or variability of individual genes.We conclude that parallel analysis of CGH and microarray data, in conjunction with known gene expression patterns, can be used to identify biomarkers with prognostic values in breast cancer.

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Section: Discussionsupporting

confidence: 63%

Concurrent Gene Signatures for Han Chinese Breast Cancers

Huang¹,

Lien

et al. 2013

PLoS ONE

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“…As PI3K-Akt and Ras-MAPK signaling pathway are the most frequently activated signaling pathways involved in gliomagenesis and TRIM45 was also reported to be associated with PKC-mediated modulation of the ERK-JNK and NF- κ B signaling pathway, 19, 20 we examined the phosphorylation status of AKT, ERK, JNK, p38, and IKK β in TRIM45-overexpressing or TRIM45 KO glioma cells. We did not detect any change in the phosphorylation status of all the kinases examined, regardless of whether the expression of TRIM45 was upregulated or downregulated (Supplementary Figures 7A and B), suggesting that TRIM45 does not affect the PI3K/AKT, MAPK, and NF- κ B signaling pathways in glioma cells.…”

Section: Resultsmentioning

confidence: 99%

“…18, 19 It also negatively regulates NF- κ B signaling. 20 Although TRIM45 mRNA is highly expressed in the brain of human adult and embryonic tissues, 18 its function in primary CNS tumors has not been investigated yet.…”

mentioning

confidence: 99%

TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination

Zhang

Cui

et al. 2017

Cell Death Dis

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Tripartite motif-containing protein 45 (TRIM45) belongs to a large family of RING-finger-containing E3 ligases, which are highly expressed in the brain. However, little is known regarding the role of TRIM45 in cancer biology, especially in human glioma. Here, we report that TRIM45 expression is significantly reduced in glioma tissue samples. Overexpression of TRIM45 suppresses proliferation and tumorigenicity in glioblastoma cells in vitro and in vivo. In addition, CRISPR/Cas9-mediated knockout of TRIM45 promotes proliferation and inhibits apoptosis in glioblastoma cells. Further mechanistic analyses show that TRIM45 interacts with and stabilizes p53. TRIM45 conjugates K63-linked polyubiquitin chain to the C-terminal six lysine residues of p53, thereby inhibiting the availability of these residues to the K48-linked polyubiquitination that targets p53 for degradation. These findings suggest that TRIM45 is a novel tumor suppressor that stabilizes and activates p53 in glioma.

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“…We speculated that TRIM45 acts as a repressor between the region downstream of PKC pathways and the nuclear factor-κB and/or MAPK signaling pathways (Supplementary Figure 4a). 36 This observation led us to hypothesize that TRIM45 can inhibit the function of RACK1 by inhibiting interaction between RACK1 and PKCβII directly, not through the ubiquitinproteosomal degradation system. Initially, we performed a co-precipitation experiment.…”

Section: Interaction Between Rack1 and Pkcβii Is Inhibited By Trim45mentioning

confidence: 98%

The TRIM-FLMN protein TRIM45 directly interacts with RACK1 and negatively regulates PKC-mediated signaling pathway

et al. 2014

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The receptor for activated C-kinase (RACK1), a scaffolding protein that participates in the protein kinase C (PKC) signaling pathway, has an important role in shuttling active PKCs to its substrate. Indeed, recent studies have revealed that RACK1 has an important role in tumorigenesis and that enhancement of the feed-forward mechanism of the c-Jun N-terminal kinase (JNK)-Jun pathway via RACK1 is associated with constitutive activation of MEK (MAPK-ERK kinase)-ERK (extracellular signal-regulated kinase) signaling in human melanoma cells. Taken together, RACK1 additionally has a very important role in the mitogen-activated protein kinase (MAPK) signaling pathway. Here, we show that one of the tripartite motif-containing (TRIM) family ubiquitin ligases, TRIM45, is a novel RACK1-interacting protein and downregulates MAPK signal transduction. Importantly, the expression of TRIM45 is induced when growth-promoting extracellular stimuli activate the MAPK signaling pathway, resulting in attenuation of activation of the MAPK pathway. These findings suggest that TRIM45 functions as a member of the negative feedback loop of the MAPK pathway.

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TRIM45 negatively regulates NF-κB-mediated transcription and suppresses cell proliferation

Cited by 42 publications

References 38 publications

Concurrent Gene Signatures for Han Chinese Breast Cancers

Concurrent Gene Signatures for Han Chinese Breast Cancers

TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination

The TRIM-FLMN protein TRIM45 directly interacts with RACK1 and negatively regulates PKC-mediated signaling pathway

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