Trans-activation Response (TAR) RNA-binding Protein 2 Is a Novel Modulator of Transient Receptor Potential Canonical 4 (TRPC4) Protein

Zimmermann, Jasmin Nicole; Latta, Lorenz; Beck, Andreas; Leidinger, Petra; Fecher‐Trost, Claudia; Schlenstedt, Gabriel; Meese, Eckart; Wissenbach, Ulrich; Flockerzi, Veit

doi:10.1074/jbc.m114.557066

Cited by 7 publications

(4 citation statements)

References 54 publications

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“…Trans-activation response RNA-binding protein 2 (Tarbp2) was reported as a modulator for TRPC4 channels. Tarbp2 binding to the C terminus of TRPC4 induced the upregulation of the channel activity and increased the cytosolic Ca 2+ concentration [ 119 ]. This resulted in a dynamic regulation of Dicer, a protein requiring Ca 2+ -dependent proteolytic activation.…”

Section: Physiological and Pathological Functions Of Trpcs Revealementioning

confidence: 99%

Transient Receptor Potential Canonical (TRPC) Channels: Then and Now

Chen

Sooch

Demaree

et al. 2020

Cells

113

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Twenty-five years ago, the first mammalian Transient Receptor Potential Canonical (TRPC) channel was cloned, opening the vast horizon of the TRPC field. Today, we know that there are seven TRPC channels (TRPC1–7). TRPCs exhibit the highest protein sequence similarity to the Drosophila melanogaster TRP channels. Similar to Drosophila TRPs, TRPCs are localized to the plasma membrane and are activated in a G-protein-coupled receptor-phospholipase C-dependent manner. TRPCs may also be stimulated in a store-operated manner, via receptor tyrosine kinases, or by lysophospholipids, hypoosmotic solutions, and mechanical stimuli. Activated TRPCs allow the influx of Ca2+ and monovalent alkali cations into the cytosol of cells, leading to cell depolarization and rising intracellular Ca2+ concentration. TRPCs are involved in the continually growing number of cell functions. Furthermore, mutations in the TRPC6 gene are associated with hereditary diseases, such as focal segmental glomerulosclerosis. The most important recent breakthrough in TRPC research was the solving of cryo-EM structures of TRPC3, TRPC4, TRPC5, and TRPC6. These structural data shed light on the molecular mechanisms underlying TRPCs’ functional properties and propelled the development of new modulators of the channels. This review provides a historical overview of the major advances in the TRPC field focusing on the role of gene knockouts and pharmacological tools.

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Section: Physiological and Pathological Functions Of Trpcs Revealementioning

confidence: 99%

Transient Receptor Potential Canonical (TRPC) Channels: Then and Now

Chen

Sooch

Demaree

et al. 2020

Cells

113

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“…Drosophila TRP or TRPL is about 40% identical to the TRPC1 and TRPC4. Intriguingly, the putative FKBP binding domain found in Drosophila TRPL is found in all the mammalian TRPC proteins as well [ 31 , 33 , 34 ].…”

Section: Fkbps and Critical Cellular Signalling Pathwaysmentioning

confidence: 99%

Comparative analysis of FKBP family protein: evaluation, structure, and function in mammals and Drosophila melanogaster

Ghartey‐Kwansah

Feng

et al. 2018

BMC Dev Biol

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BackgroundFK506-binding proteins (FKBPs) have become the subject of considerable interest in several fields, leading to the identification of several cellular and molecular pathways in which FKBPs impact prenatal development and pathogenesis of many human diseases.Main bodyThis analysis revealed differences between how mammalian and Drosophila FKBPs mechanisms function in relation to the immunosuppressant drugs, FK506 and rapamycin. Differences that could be used to design insect-specific pesticides. (1) Molecular phylogenetic analysis of FKBP family proteins revealed that the eight known Drosophila FKBPs share homology with the human FKBP12. This indicates a close evolutionary relationship, and possible origination from a common ancestor. (2) The known FKBPs contain FK domains, that is, a prolyl cis/trans isomerase (PPIase) domain that mediates immune suppression through inhibition of calcineurin. The dFKBP59, CG4735/Shutdown, CG1847, and CG5482 have a Tetratricopeptide receptor domain at the C-terminus, which regulates transcription and protein transportation. (3) FKBP51 and FKBP52 (dFKBP59), along with Cyclophilin 40 and protein phosphatase 5, function as Hsp90 immunophilin co-chaperones within steroid receptor-Hsp90 heterocomplexes. These immunophilins are potential drug targets in pathways associated with normal physiology and may be used to treat a variety of steroid-based diseases by targeting exocytic/endocytic cycling and vesicular trafficking. (4) By associating with presinilin, a critical component of the Notch signaling pathway, FKBP14 is a downstream effector of Notch activation at the membrane. Meanwhile, Shutdown associates with transposons in the PIWI-interacting RNA pathway, playing a crucial role in both germ cells and ovarian somas. Mutations in or silencing of dFKBPs lead to early embryonic lethality in Drosophila. Therefore, further understanding the mechanisms of FK506 and rapamycin binding to immunophilin FKBPs in endocrine, cardiovascular, and neurological function in both mammals and Drosophila would provide prospects in generating unique, insect specific therapeutics targeting the above cellular signaling pathways.ConclusionThis review will evaluate the functional roles of FKBP family proteins, and systematically summarize the similarities and differences between FKBP proteins in Drosophila and Mammals. Specific therapeutics targeting cellular signaling pathways will also be discussed.

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“…Moreover, many studies have further reported that TARBP2 plays an oncogenic or tumor suppressor role in many tumors, both in vitro and in vivo [10,12,13,22]. Decreased expression of TARBP2 results in miRNA decreases in human cancers [12,[29][30][31]. However, further studies are required to investigate the underlying molecular mechanisms of TARBP2 in human cancers.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-induced let-7f-5p/TARBP2 feedback loop regulates osteosarcoma cell proliferation and invasion by inhibiting the Wnt signaling pathway

Chen

Fang

et al. 2020

Aging

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Osteosarcoma (OS) is the most common bone tumor in children and adolescents and is characterized by high metastatic and recurrence rates. In the past, it has been shown that microRNAs may play critical roles in hypoxia-related OS proliferation and invasion. However, the mechanisms by which OS cells acquire this malignant phenotype have remained largely unknown. In the present study, we report that let-7f-5p and TARBP2 were expressed in lower amounts in human OS cell lines when compared with the hFOB normal human osteoblastic cell line; however, both types of cells were repressed by hypoxia. let-7f-5p and TARBP2 significantly inhibited the proliferation and invasion of OS cells. Furthermore, TARBP2 as a downstream and functional target of let-7f-5p regulated the expression of let-7f-5p, and there was a regulatory feedback loop between let-7f-5p and TARBP2. This loop reduced the expression of let-7f-5p and TARBP2 in OS cells to a very low level, which was induced by hypoxia. Furthermore, the hypoxia-induced let-7f-5p/TARBP2 feedback loop contributed to activation of the Wnt signaling pathway. Taken together, our data clearly showed that the feedback loop between let-7f-5p and TARBP2 induced by the hypoxia-promoted OS cell malignant phenotype increased with activation of the Wnt signaling pathway.

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Trans-activation Response (TAR) RNA-binding Protein 2 Is a Novel Modulator of Transient Receptor Potential Canonical 4 (TRPC4) Protein

Cited by 7 publications

References 54 publications

Transient Receptor Potential Canonical (TRPC) Channels: Then and Now

Transient Receptor Potential Canonical (TRPC) Channels: Then and Now

Comparative analysis of FKBP family protein: evaluation, structure, and function in mammals and Drosophila melanogaster

Hypoxia-induced let-7f-5p/TARBP2 feedback loop regulates osteosarcoma cell proliferation and invasion by inhibiting the Wnt signaling pathway

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