{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FAM83G (also known as PAWS1) is emerging as a multifunctional protein that plays diverse roles in both normal physiology and disease. In the context of bone morphogenetic protein (BMP) signaling, FAM83G interacts directly with SMAD1 in a SMAD4‐independent manner and becomes phosphorylated by BMPR1A, an event that is crucial for the activation of a subset of non‐canonical BMP target genes (such as NEDD9 and ASNS). These findings not only highlight its role as the first non‐SMAD substrate for type I BMP receptor kinases but also suggest that FAM83G modulates gene expression beyond the classical BMP pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, FAM83G is integral to the regulation of the cytoskeletal machinery. It is involved in controlling actin organization and focal adhesion dynamics by dynamically interacting with the actin/cytoskeletal regulator CD2AP, thereby affecting cellular migration and proper lamellipodial formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " This function appears to be conserved in cell types where cytoskeletal remodeling is fundamental for mobility.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Aberrant expression of FAM83G has been implicated in tumorigenesis. For instance, in hepatocellular carcinoma, overexpression of FAM83G not only predicts poor prognosis but also promotes cell proliferation, migration, and invasion by activating the PI3K/AKT signaling cascade and inducing epithelial to mesenchymal transition (EMT) markers (e.g., decreased E‐cadherin and increased N‐cadherin and Snail)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In a similar vein, analyses in dogs and mice have demonstrated that genetic variants in FAM83G contribute to alterations in hair follicle morphogenesis and hair cycle progression by interfacing with temporally and spatially coordinated Wnt and BMP signaling, thereby affecting hair type and structure."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, the phosphorylation status of FAM83G, especially at serine 356, modulates downstream targets such as heat shock protein 27 (HSP27), influencing apoptosis and overall cell survival. Such modulation is mediated via interactions with kinases like PKD1/PKCμ, suggesting that modifications in FAM83G can impact cell fate decisions in certain cancer contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In metastatic melanoma, FAM83G functions as a downstream effector of BMP6‐SMAD5 signaling, where it contributes critically to actin‐dependent cytoskeletal dynamics and promotes cell migration, linking its role in signal transduction with cancer metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additional evidence points to FAM83G’s role in modulating the stability of other proteins. For example, its binding to CK1α appears to protect the latter from degradation in response to immunomodulatory imide drugs (IMiDs), thereby highlighting the importance of its interactions within multiprotein complexes in determining the fate and function of associated proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, studies in domestic animals such as Meishan pigs have revealed that specific mutations in FAM83G are associated with distinct phenotypic traits, such as coat pigmentation, emphasizing the biological impact of FAM83G variants on tissue-specific functions and morphology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings characterize FAM83G/PAWS1 as a versatile regulator involved in BMP signaling, cytoskeletal organization, apoptosis, and oncogenic processes. Its ability to interact with key signaling molecules and cytoskeletal regulators underscores its potential as a therapeutic target in diverse diseases including cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Janis Vogt, Kevin S Dingwell, Lina Herhaus, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Open Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1098/rsob.130210"}], "href": "https://doi.org/10.1098/rsob.130210"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24554596"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24554596"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Timothy D Cummins, Kevin Z L Wu, Polyxeni Bozatzi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.202390"}], "href": "https://doi.org/10.1242/jcs.202390"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29175910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29175910"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Chen Liu, Xuan-Yu Huang, Yun Huang "}, {"type": "b", "children": [{"type": "t", "text": "FAM83G promotes proliferation, invasion, and metastasis by regulating PI3K/AKT signaling in hepatocellular carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2021.05.081"}], "href": "https://doi.org/10.1016/j.bbrc.2021.05.081"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34144502"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34144502"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Pierre Balmer, Auxanne K Fellay, Beyza S Sayar, et al. 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