{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRAB39A has emerged as a critical regulator of unconventional cytokine secretion. In monocytic cells, RAB39A directly interacts with caspase‑1, and its activity proves essential for the secretion of the pro‐inflammatory cytokine interleukin‑1β. Knockdown experiments demonstrated that reduced RAB39A expression results in decreased IL‑1β release, while overexpression, particularly of forms resistant to caspase‑1 cleavage, further enhances secretion. This identifies RAB39A as a key trafficking adaptor that couples caspase‑1 activity with IL‑1β release."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of intracellular infection, RAB39A functions in the regulation of late endocytic vesicle trafficking. It localizes predominantly to multivesicular bodies that move along microtubules and is actively recruited to chlamydial inclusions throughout the bacterial life cycle. By facilitating the delivery of host sphingolipids and other essential lipids from these vesicles to the inclusion membrane, RAB39A promotes inclusion maturation and, consequently, chlamydial replication and infectivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in inflammation and host–pathogen interactions, RAB39A is implicated in a broader array of vesicular trafficking pathways that impact fundamental cellular processes. Although studies on a closely related isoform (Rab39b) have linked dysregulation of macroautophagy to neurodegeneration via its association with a C9ORF72–SMCR8–WDR41 complex, RAB39A itself is known to modulate key signaling pathways—including Hippo and Notch—as well as microtubule organization, neuronal differentiation, and autophagy/mitophagy. Additionally, recent evidence points to its emerging oncogenic function, where RAB39A contributes to cancer stemness and tumorigenesis through associations with transcriptional regulators such as RXRB, NCOR, and HDAC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christine E Becker, Emma M Creagh, Luke A J O'Neill "}, {"type": "b", "children": [{"type": "t", "text": "Rab39a binds caspase-1 and is required for caspase-1-dependent interleukin-1beta secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.046102"}], "href": "https://doi.org/10.1074/jbc.M109.046102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19833722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19833722"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Julian Gambarte Tudela, Anahi Capmany, Maryse Romao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The late endocytic Rab39a GTPase regulates the interaction between multivesicular bodies and chlamydial inclusions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.170092"}], "href": "https://doi.org/10.1242/jcs.170092"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26163492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26163492"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Camille Corbier, Chantal Sellier "}, {"type": "b", "children": [{"type": "t", "text": "C9ORF72 is a GDP/GTP exchange factor for Rab8 and Rab39 and regulates autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Small GTPases (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21541248.2016.1212688"}], "href": "https://doi.org/10.1080/21541248.2016.1212688"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27494456"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27494456"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tokuhiro Chano, Sofia Avnet "}, {"type": "b", "children": [{"type": "t", "text": "RAB39A: a Rab small GTPase with a prominent role in cancer stemness."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jb/mvy041"}], "href": "https://doi.org/10.1093/jb/mvy041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29648608"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29648608"}]}]}]}