The E3 ubiquitin ligase TRIM25 regulates adipocyte differentiation via proteasome-mediated degradation of PPARγ

Lee, Jae Min; Choi, Sun Sil; Lee, Yo Han; Khim, Keon Woo; Yoon, Susan A.; Kim, Byung-gyu; Nam, Dougu; Suh, Pann‐Ghill; Myung, Kyungjae; Choi, Jang Hyun

doi:10.1038/s12276-018-0162-6

Cited by 33 publications

(41 citation statements)

References 54 publications

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“…To our knowledge, C 7 is the only key residue on the domain that has not been individually mutated for this purpose. However, it has been shown that simultaneous mutations on either C 1 +C 7 or C 6 +C 7 abolish the ligase activity of AMFR and some TRIM family members, respectively (Wang et al, 2014;Liu et al, 2017a;Lee et al, 2018a). As shown in Figure 3, many E3 ligases have been inactivated by simultaneous mutations on C 1 +C 2 .…”

Section: Inactivating Ring-type E3s By Mutating the Zinc-coordinatingmentioning

confidence: 99%

How to Inactivate Human Ubiquitin E3 Ligases by Mutation

Garcia-Barcena

Osinalde

Ramírez

et al. 2020

Front. Cell Dev. Biol.

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E3 ubiquitin ligases are the ultimate enzymes involved in the transfer of ubiquitin to substrate proteins, a process that determines the fate of the modified protein. Numerous diseases are caused by defects in the ubiquitin-proteasome machinery, including when the activity of a given E3 ligase is hampered. Thus, inactivation of E3 ligases and the resulting effects at molecular or cellular level have been the focus of many studies during the last few years. For this purpose, site-specific mutation of key residues involved in either protein interaction, substrate recognition or ubiquitin transfer have been reported to successfully inactivate E3 ligases. Nevertheless, it is not always trivial to predict which mutation(s) will block the catalytic activity of a ligase. Here we review over 250 sitespecific inactivating mutations that have been carried out in 120 human E3 ubiquitin ligases. We foresee that the information gathered here will be helpful for the design of future experimental strategies.

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Section: Inactivating Ring-type E3s By Mutating the Zinc-coordinatingmentioning

confidence: 99%

How to Inactivate Human Ubiquitin E3 Ligases by Mutation

Garcia-Barcena

Osinalde

Ramírez

et al. 2020

Front. Cell Dev. Biol.

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“…TRIM25 is a RNA-binding protein and belongs to the Tripartite Motif (TRIM) family of E3 ubiquitin ligases, which catalyzes the addition of polyubiquitin chains to its substrates for degradation [30][31][32][33] . We performed co-immunoprecipitation (Co-IP) analysis and results showed TRIM25 bound with all three IGF2BPs ( Fig.…”

Section: Trim25 Is the E3 Ligase That Mediates Igf2bps Ubiquitinationmentioning

confidence: 99%

circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity

et al. 2021

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Circular RNAs (circRNA) are a class of covalently closed single-stranded RNAs that have been implicated in cancer progression. Here we identify circNDUFB2 to be downregulated in non-small cell lung cancer (NSCLC) tissues, and to negatively correlate with NSCLC malignant features. Elevated circNDUFB2 inhibits growth and metastasis of NSCLC cells. Mechanistically, circNDUFB2 functions as a scaffold to enhance the interaction between TRIM25 and IGF2BPs, a positive regulator of tumor progression and metastasis. This TRIM25/circNDUFB2/IGF2BPs ternary complex facilitates ubiquitination and degradation of IGF2BPs, with this effect enhanced by N6-methyladenosine (m6A) modification of circNDUFB2. Moreover, circNDUFB2 is also recognized by RIG-I to activate RIG-I-MAVS signaling cascades and recruit immune cells into the tumor microenvironment (TME). Our data thus provide evidences that circNDUFB2 participates in the degradation of IGF2BPs and activation of anti-tumor immunity during NSCLC progression via the modulation of both protein ubiquitination and degradation, as well as cellular immune responses.

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“…TRIM25 possesses E3 ligase activity (Zang et al, 2017; Lee et al, 2018; Li et al, 2018). TRIM25 expression levels affected the protein expression of PTEN.…”

Section: Resultsmentioning

confidence: 99%

“…TRIM25 acted on AKT signaling to modulate the resistance of HCC cells to EPI. Lastly, TRIM25 was an ubiquitin E3 ligase for PPARγ and metastasis‐associated 1 protein (Zang et al, 2017; Lee et al, 2018; Li et al, 2018). In the current study, we demonstrated that TRIM25 bound to PTEN and TRIM25 knockdown inhibited PTEN ubiquitination (Figure 5), and suggested a potential regulatory mechanism of TRIM25 on PTEN/AKT pathway.…”

Section: Discussionmentioning

confidence: 99%

Tripartite motif protein 25 is associated with epirubicin resistance in hepatocellular carcinoma cells via regulating PTEN/AKT pathway

Yuan¹,

Zheng²,

Tang³

2020

Cell Biology International

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Tripartite motif protein 25 (TRIM25) expression was altered in various human cancers. Herein, we found that the expression of TRIM25 was elevated in hepatocellular carcinoma (HCC) tissues and cell lines. Knockdown of TRIM25 increased the sensitivity of HCC HepG2 cells to epirubicin (EPI), as indicated by reduced cell viability, enhanced cell apoptosis, and downregulated P‐glycoprotein (P‐gp) and multiple drug‐resistance protein 1 (MRP1). Moreover, TRIM25 knockdown strengthened the effects of EPI on phosphatase and tensin homolog (PTEN) and phosphorylated (p)‐AKT. However, overexpression of TRIM25 exerted an opposite effect, weakening the sensitivity of Huh7 to EPI, and obviously increasing PTEN and reducing p‐AKT. Most important, all the changes induced by TRIM25 overexpression in Huh7 were reversed with additional treatment of LY294002 (an AKT pathway inhibitor). Notably, coimmunoprecipitation experiments confirmed the interaction between TRIM25 and PTEN. Knockdown of TRIM25 resulted in reduced ubiquitination of PTEN protein. Collectively, our data suggested that TRIM25 enhanced EPI resistance via modulating PTEN/AKT pathway, and targeting TRIM25 may enhance the sensitivity of HCC cells toward chemotherapy drugs.

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The E3 ubiquitin ligase TRIM25 regulates adipocyte differentiation via proteasome-mediated degradation of PPARγ

Cited by 33 publications

References 54 publications

How to Inactivate Human Ubiquitin E3 Ligases by Mutation

How to Inactivate Human Ubiquitin E3 Ligases by Mutation

circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity

Tripartite motif protein 25 is associated with epirubicin resistance in hepatocellular carcinoma cells via regulating PTEN/AKT pathway

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