{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRITA1, the RBP‐J–interacting and tubulin‐associated protein, plays a pivotal role in the negative regulation of Notch signaling by binding to the transcription factor RBP‐J (CSL) and promoting its export from the nucleus. Structural, biochemical, and biophysical investigations have revealed that RITA1 engages RBP‐J via interaction domains that are reminiscent of the Notch RAM region, thereby interfering with the assembly of transcriptional activator complexes and reducing the expression of Notch target genes. This mechanistic insight helps explain its function as a molecular switch in modulating cellular responses governed by Notch."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in Notch pathway modulation, RITA1 exhibits complex, context‐dependent functions in tumor biology. In hepatocellular carcinoma, elevated levels of RITA1 suppress cell proliferation and promote early apoptosis through upregulation of p53, downregulation of cyclins, and induction of cell cycle arrest, suggesting a tumor‐suppressive role. In contrast, aberrantly high expression of RITA1 in bladder cancer appears to drive tumor growth by recruiting the E3 ubiquitin ligase TRIM25 to facilitate the ubiquitination and proteasomal degradation of RBP‐J, thereby dampening Notch signaling and its downstream targets. These studies underscore the multifaceted functions of RITA1 in cancer, where its impact may vary with cellular context."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond transcriptional regulation, RITA1 is instrumental in governing cell dynamics and cytoskeletal organization. Its association with tubulin underlies its ability to affect microtubule stability, focal adhesion turnover, and actin cytoskeleton remodeling—key processes that regulate cell migration and invasion. In mitosis, RITA1 modulates the activity of the mitotic kinase Aurora A by influencing the microtubule binding of its activator TPX2, thereby contributing to proper spindle pole formation and cell cycle progression. Moreover, in the context of placental development, RITA1 is essential for trophoblast migration, invasion, and fusion, and its reduced expression is associated with early‐onset preeclampsia. Emerging data also indicate that dysregulation of RITA1 may affect treatment responses in anal squamous cell carcinoma, further emphasizing its broad biological impact."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nassif Tabaja, Zhenyu Yuan, Franz Oswald, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure-function analysis of RBP-J-interacting and tubulin-associated (RITA) reveals regions critical for repression of Notch target genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M117.791707"}], "href": "https://doi.org/10.1074/jbc.M117.791707"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28487372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28487372"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Birgit Brockmann, Helena Mastel, Franz Oswald, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of the interaction between human RITA and Drosophila Suppressor of Hairless."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hereditas (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/hrd2.00074"}], "href": "https://doi.org/10.1111/hrd2.00074"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25588307"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25588307"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Haihe Wang, Guofu Chen, Hongzhi Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RITA inhibits growth of human hepatocellular carcinoma through induction of apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3727/096504013x13685487925059"}], "href": "https://doi.org/10.3727/096504013x13685487925059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24308154"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24308154"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Haihe Wang, Zhanchun Yang, Chunbo Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RBP-J-interacting and tubulin-associated protein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma by activating the p53-Fbxw7 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2014.10.023"}], "href": "https://doi.org/10.1016/j.bbrc.2014.10.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25445601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25445601"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Huancheng Tang, Xiangdong Li, Lijuan Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RITA1 drives the growth of bladder cancer cells by recruiting TRIM25 to facilitate the proteasomal degradation of RBPJ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.15459"}], "href": "https://doi.org/10.1111/cas.15459"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35701858"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35701858"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Samira Catharina Hoock, Andreas Ritter, Kerstin Steinhäuser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RITA modulates cell migration and invasion by affecting focal adhesion dynamics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.12551"}], "href": "https://doi.org/10.1002/1878-0261.12551"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31353815"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31353815"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Nina-Naomi Kreis, Kerstin Steinhäuser, Andreas Ritter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Potential involvement of RITA in the activation of Aurora A at spindle poles during mitosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-019-0716-7"}], "href": "https://doi.org/10.1038/s41388-019-0716-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30705408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30705408"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Julia Maria Wildner, Alexandra Friemel, Lukas Jennewein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RITA Is Expressed in Trophoblastic Cells and Is Involved in Differentiation Processes of the Placenta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells8121484"}], "href": "https://doi.org/10.3390/cells8121484"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31766533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31766533"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Franz Rödel, Kerstin Steinhäuser, Nina-Naomi Kreis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prognostic impact of RITA expression in patients with anal squamous cell carcinoma treated with chemoradiotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Radiother Oncol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.radonc.2017.10.028"}], "href": "https://doi.org/10.1016/j.radonc.2017.10.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29122359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29122359"}]}]}]}