{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSTRAP is a multifunctional scaffold protein that modulates key signaling pathways governing cell proliferation, apoptosis, and stress responses. In several contexts, STRAP interacts directly with proteins such as NM23‐H1, PDK1, ASK1, and B‑MYB to inhibit transforming growth factor‑β (TGF‑β) signaling and to promote p53‐mediated responses. By facilitating the assembly of p53 coactivator complexes (involving p300) and antagonizing negative regulators, STRAP contributes to gene transcription control through Sp1‐dependent mechanisms, thereby affecting cell cycle regulators like p21(Cip1) and cell adhesion molecules such as E‑cadherin. These molecular interactions underline its role in modulating both TGF‑β and p53 pathways, which are crucial for maintaining the balance between cell survival and apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in these classical tumor suppressor and growth regulatory pathways, STRAP has emerged as a critical modulator of oncogenic developmental signaling. In colorectal and other cancers, STRAP supports cancer stem cell maintenance and tumor progression by antagonizing the assembly of chromatin modifiers such as PRC2 to epigenetically activate NOTCH signaling. Moreover, STRAP interferes with the formation of the β‑catenin destruction complex through binding to GSK3β and Axin, leading to β‑catenin stabilization and enhanced transcription of proliferation‐ and metastasis‐associated target genes. Elevated STRAP levels have been implicated in intestinal tumor initiation in the context of APC mutations and are observed in hepatocellular carcinoma and neuroblastoma, underscoring its role in aberrant activation of NOTCH and Wnt/β‑catenin pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its nuclear signaling functions, STRAP also plays roles in the post‑transcriptional regulation of gene expression and cellular metabolism. By being tethered to specific mRNAs—such as collagen transcripts via interaction with LARP6—STRAP restricts their translation to ensure coordinated synthesis of collagen polypeptides. Its association with RNA‑binding factors like Csde1 further influences the expression of transcripts critical for erythroid differentiation and the response to hypoxic stress. Moreover, STRAP can localize to mitochondria, where its interaction with ATP synthase downregulates mitochondrial ATP production, thereby sensitizing cancer cells to apoptotic stimuli under energy‑limiting conditions. Notably, context‑dependent roles have been observed, as reduced STRAP expression in hepatocellular carcinoma correlated with enhanced PTEN degradation and tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hyun-A Seong, Haiyoung Jung, Hyunjung Ha "}, {"type": "b", "children": [{"type": "t", "text": "NM23-H1 tumor suppressor physically interacts with serine-threonine kinase receptor-associated protein, a transforming growth factor-beta (TGF-beta) receptor-interacting protein, and negatively regulates TGF-beta signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M609832200"}], "href": "https://doi.org/10.1074/jbc.M609832200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17314099"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17314099"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hyun-A Seong, Haiyoung Jung, Hueng-Sik Choi, et al. 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