{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTOB1 is a multifunctional regulator of mRNA turnover that acts at the post‐transcriptional level. It enhances deadenylation by physically bridging the poly(A) tail–bound poly(A)‐binding protein (PABPC1) and deadenylase complexes such as CCR4–CAF1, as well as by interacting with sequence‐specific RNA regulators (e.g. CPEB3) to recruit Caf1, thereby promoting rapid mRNA decay and controlling gene expression (typically of growth‐promoting factors) in quiescent or stimulated cells. Its structured N‐terminal BTG/Tob domain and unstructured C‐terminal PAM2 motifs are key for these interactions, and the stability of TOB1 itself is governed by ubiquitin–proteasome degradation mechanisms and can be modulated by stress conditions that target these regulatory regions (e.g. oxidative stress)."}, {"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": "\nIn a wide spectrum of cancers, TOB1 is frequently implicated as a tumor suppressor by inhibiting cell cycle progression and impairing proliferation, migration, and invasion. Its anti‐proliferative activities are executed through several key signaling pathways – including MAPK/ERK, TGF‑β/Smad, β‑catenin and calcium signaling – and by downregulating oncogenic transcripts such as c‑myc. Dysregulation of TOB1 occurs via phosphorylation (which can impair its growth‐inhibitory capability), altered subcellular localization, and targeted degradation (for instance, via the SCF–Skp2 complex). Moreover, aberrant microRNA regulation (e.g. by miR‑25, miR‑371‑3p, miR‑125‑13p and even a miR‑590–mediated mechanism in immune cells) further contributes to reduced or functionally inactivated TOB1 in gastric, lung, breast, esophageal, colon and pancreatic cancers – with some contexts even revealing an oncogenic role when cytoplasmic accumulation reinforces β‑catenin signaling. These findings together underscore the context‐dependent role of TOB1 in tumorigenesis and cancer progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in mRNA metabolism and tumor suppression, TOB1 also exerts critical immunomodulatory functions. In T lymphocytes, for example, it can suppress interleukin‑2 translation through interactions with inducible poly(A)‑binding proteins and downregulate pro‑activation factors such as Tsg. This inhibition contributes to the attenuation of Th17 differentiation and may modulate inflammatory responses in autoimmune conditions, thereby linking TOB1 function not only to cell proliferation and cancer but also to immune homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "35"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nader Ezzeddine, Tsung-Cheng Chang, Wenmiao Zhu, et al. 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