Experimental immunology Potential role of RING finger protein 166 (RNF166), a member of an ubiquitin ligase subfamily, involved in regulation of T cell activation

50 Background: hypovitaminosis D is frequent in renal diseases but it was never reported in metastatic renal cell carcinoma (mRCC). The interaction between vitamin D and its receptor (VDR) has a key role for T-cell activation. Naïve T-cells do not express VDR and had very low expression of phospholipase C-γ1 (PLC-γ1), with low responsiveness to T-cell receptor (TCR). Initial TCR signaling induces VDR expression and upregulates PLC-γ1 via the kinase p38 pathway. VDR interaction with high concentrations of vitamin D and PLC-γ1 increase are required to trigger classical TCR signaling, increasing T-cell responsiveness. On these basis, we hypothesized that hypovitaminosis D could contribute to lower responsiveness to immune-checkpoint inhibitors (CKI). Methods: we assessed vitamin D levels of mRCC patients undergoing therapy with CKI, with the aim to reveal hypovitaminosis D, evaluate its prevalence and hypothesize its potential role in the outcome of treatment with CKI. Results: of 10 mRCC patients pretreated with tyrosine-kinase inhibitors, vitamin D levels assessed before the first treatment with nivolumab (anti-PD1 CKI) revealed deficiency in 80% of cases (8 patients). Hypovitaminosis D was severe ( < 20 ng/ml) in 7 cases and moderate ( < 30 ng/ml) in one. The 2 patients without deficiency (20%), had vitamin D values near to the lower limit of normality. Oral supplementation with cholecalciferol was given when necessary, likely confounding the possible influence of vitamin D deficiency on the outcome of CKI treatment. Vitamin D normal values after two months of therapy were recovered in the great majority of cases. Interestingly, the only patient who achieved a good objective response to treatment had normal values of vitamin D before therapy. Conclusions: hypovitaminosis D could have a relevant prevalence in mRCC patients. Considering the role of vitamin D in T-cell activation, assessment of its levels and initiation of a supplementation before immunotherapy should be considered to enhance responsiveness. On the basis of these observations, we are planning a perspective multicenter study to investigate the role of hypovitaminosis D in mRCC patients treated with CKI (PRoviDenCe study).

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A potential role of UBC28 interacting RING finger protein TaRF1 in spike development of wheat

Journal of Plant Biochemistry and Biotechnology ◽

10.1007/s13562-013-0227-5 ◽

2013 ◽

Vol 23 (4) ◽

pp. 421-429 ◽

Cited By ~ 3

Author(s):

Min Jeong Hong ◽

Yong Weon Seo

Keyword(s):

Potential Role ◽

Ring Finger ◽

Ring Finger Protein ◽

Finger Protein ◽

Spike Development

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RNF6 as an Oncogene and Potential Therapeutic Target—A Review

BioTech ◽

10.3390/biotech9040022 ◽

2020 ◽

Vol 9 (4) ◽

pp. 22

Author(s):

Paweł Zapolnik ◽

Antoni Pyrkosz

Keyword(s):

Ubiquitin Ligase ◽

Therapeutic Target ◽

Human Cancer ◽

Ring Finger ◽

Model Organisms ◽

Ring Finger Protein ◽

Potential Therapeutic Target ◽

Finger Protein ◽

Potential Prognostic Factor

The RNF6 gene encodes Ring Finger Protein 6 (RNF6), which functions as a ubiquitin ligase. Its functions are not entirely known, but research shows that it is involved in human cancer development. Initially, this gene was considered to be a tumor suppressor. Numerous statistical analyses on cell lines and animals indicate, however, that RNF6 functions as an oncogene, involved in signaling pathways, including SHP1/STAT3, AKT/mTOR, Wnt/β-catenin, or ERα/Bcl-xL. Due to this fact, it has become a potential prognostic factor and therapeutic target. Studies in tumor cells and model organisms using inhibitors such as total saponins from Paris forrestii (TSPf), ellagic acid, or microRNA molecules show the effectiveness of inhibiting RNF6, and through it, the pathways of tumor cell proliferation. The results of the currently available studies are promising, but the function of RNF6 is not fully understood. More research is needed to assess the role of RNF6 and to check the safety and efficacy of inhibitors.

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