Ask about this productRelated genes to: RAB22A antibody
- Gene:
- RAB22A NIH gene
- Name:
- RAB22A, member RAS oncogene family
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 20q13.32
- Locus Type:
- gene with protein product
- Date approved:
- 2000-05-31
- Date modifiied:
- 2016-10-05
Related products to: RAB22A antibody
Related articles to: RAB22A antibody
- Viral infections trigger complex host defense responses, yet many key regulatory mechanisms remain undefined. Here, we identify the RNA-binding protein RBM25 as a potent, broad-spectrum host antiviral factor, independently of the type I interferon (IFN-I) pathway. Viral infection downregulates RBM25 expression, and RBM25-deficient mice exhibit enhanced susceptibility to multiple viruses and more aggravated tissue damage. In vitro, RBM25 inhibits the viral infection and replication across a spectrum of RNA and DNA viruses. Mechanistically, the antiviral activity of RBM25 is independent of IFN-I signaling and is instead linked to an early blockade in the viral life cycle. RBM25 specifically impedes viral cell entry through the suppression of the host GTPase Rab22a, a well-known facilitator of viral endocytosis. Virus infection-elicited downregulation of RBM25 results in Rab22a upregulation, which consequently potentiates viral entry. Furthermore, we elucidate the post-transcriptional mechanisms that RBM25 interacts with RC3H1 (ring finger and CCCH-type domains 1) to form an RNA-binding complex that binds and destabilizes Rab22a mRNA, thereby limiting its protein translation. Collectively, our work unveils the RBM25/RC3H1-Rab22a axis as an interferon-independent post-transcriptional pathway that governs viral entry by modulating the mRNA stability of a critical host endocytosis factor, which presents a potential target for developing broad-spectrum antiviral strategies. - Source: PubMed
Publication date: 2026/06/16
Ding YingyingChen HuiyingJiang YuyuZhao ChunyanBai JieXiang YanWang ZetingWang XixiRui BingTang WandaDing YueZhan ZhenzhenZhang YunkaiLiu Xingguang - Mammalian Atg8-family (ATG8) proteins are crucial for macroautophagic/autophagic degradation in the lysosome and facilitate non-degradative processes including multiple distinct forms of unconventional protein secretion. These secretion pathways, collectively termed secretory autophagy, depend upon ATG8 conjugated to membranes to both specify and traffic molecules for extracellular release. Here, we review the current understanding of how membrane ATG8ylation supports secretory autophagy, and propose a cell biological framework for classifying the growing repertoire of secretory autophagy pathways based on membrane ATG8ylation at discrete intracellular vesicular intermediates. Finally, we detail the emerging roles of these pathways in physiology and disease.: Aβ, amyloid-β; Acb1, acyl-coA-binding 1; ALS, amyotrophic lateral sclerosis; APP, amyloid beta precursor protein; APEX2, ascorbate peroxidase; ATG, autophagy related; AWOL, autophagosome-mediated exit without lysis; BafA1, bafilomycin A; BirA*, mutant BirA biotin ligase; BMI, body-mass index; CASM, ATG8 conjugation at single membranes; DAMPs, danger/damage-associated molecular patterns; DBI, diazepam binding inhibitor, acyl-CoA binding protein; DSS, dextran sodium sulfate; ER, endoplasmic reticulum; ERGIC, endoplasmic reticulum intermediate compartment; ESCRT, endosomal complexes required for transport; EVs, extracellular vesicles; EVPs, extracellular vesicles and particles; HMGB1, high mobility group box 1; IDE, insulin degrading enzyme; IFNB, interferon beta; ILV, intralumenal vesicles; LANDO, LC3-associated endocytosis; LAP, LC3-associated phagocytosis; LIR, LC3 interacting region; LDELS, LC3-dependent EV loading and secretion; LLOMe, L-leucyl-L-leucine methyl ester hydrobromide; M2, influenza A virus matrix 2, MAD, migratory autolysosome disposal; miRNAs, microRNAs; M-MDSC, monocytic myeloid derived suppressor cells; MVEs, multivesicular endosomes; PAMPs, pathogen-associated molecular patterns; P-bodies, processing bodies; PE, phosphatidylethanolamine; PD, Parkinson disease; PS, phosphatidylserine; RBPs, RNA binding proteins; R-EV, RAB22A-induced extracellular vesicle; SLC2A1, solute carrier family 2 member 1; TFRC, transferrin receptor; TGN, trans-Golgi network; TMED10, transmembrane p24 trafficking protein 10; THU, TMED10-channeled unconventional secretion; SALI, secretory autophagy during lysosome inhibition; SCF, SKP1-CUL1-F-box; SNAREs, soluble NSF attachment protein receptors. - Source: PubMed
Publication date: 2026/05/24
Debnath JayantaLeidal Andrew M - N6-methyladenosine (mA) modification has emerged as a critical post-transcriptional regulatory mechanism in osteoarthritis (OA). However, the contribution of mA-dependent regulation of circular RNAs (circRNAs) to chondrocyte senescence and OA progression remains poorly understood. We aimed to elucidate whether mA-mediated control of circRNAs regulates chondrocyte senescence and to define the underlying molecular mechanisms contributing to OA progression. Here, we identified an OA-associated circRNA, circHIPK2, and demonstrated that its abundance and function are regulated by an mA reader-dependent decay mechanism. circHIPK2 expression was reduced in human OA cartilage, and its depletion exacerbated chondrocyte senescence, increased senescence-associated secretory phenotype (SASP) gene expression, and impaired autophagy both in vitro and in the destabilization of the medial meniscus (DMM) model. Mechanistically, YTH N-methyladenosine RNA-binding protein 2 (YTHDF2) recognized mA-modified circHIPK2 and facilitated its degradation, thereby reducing circHIPK2 stability. Functionally, circHIPK2 directly interacted with RAB22A. Loss of circHIPK2 weakened this interaction, enhanced RAB22A-PI3K association, activated the PI3K-AKT-mTOR signaling pathway, disrupted autophagic flux, and accelerated senescence-associated phenotypes. Notably, the protective effects of circHIPK2 were abolished in RAB22A-binding-deficient circHIPK2 mutants, establishing a direct link between molecular interaction and functional outcome. Furthermore, we encapsulated circHIPK2 into lipid nanoparticles (circHIPK2-LNP) for transient intra-articular delivery. Intra-articular administration of circHIPK2-LNP attenuated chondrocyte senescence and alleviated OA progression in DMM mice. Collectively, mA-dependent YTHDF2-mediated degradation of circHIPK2 promotes chondrocyte senescence and OA progression by disrupting autophagy, identifying circHIPK2 as a potential therapeutic target and prognostic biomarker for cartilage aging in OA. - Source: PubMed
Publication date: 2026/03/27
Long DianboLin ZhencanLi ZhiwenLi MingZhao XiaoyiDeng ZengfaJiang ZongruiLi WeiZhong YanlinHe AishanXu YiyangMao GupingKang Yan - Chemoresistance is not only related to tumor cells themselves, but also regulated by the interaction between cells in the tumor microenvironment (TME). However, the underlying mechanisms are not well understood. RAB22A, a member of the RAB family of small GTPases that was identified by our group previously as an oncogene in colorectal cancer (CRC). In this study, we demonstrated that elevated expression of RAB22A in CRC cells, particularly in chemoresistant CRC cells, is associated with increased exosome secretion and enhanced chemoresistance. Mechanistically, RAB22A augments exosome secretion by inhibiting the ubiquitination and degradation of pyruvate kinase type M2 (PKM2), then promoting the phosphorylation of synaptosome-associated protein 23 (SNAP-23). Furthermore, RAB22A not only directly promotes chemoresistance in CRC cells but also indirectly induces acquired drug resistance of other CRC cells in the TME by promoting the secretion of RAB22A-PKM2-rich exosomes, thereby triggering intercellular chemoresistance transmission. Together, we reveal an essential role of RAB22A-PKM2-SNAP-23 signaling cascade in exosome induction in chemoresistant CRC cells and intercellular chemoresistance transmission, highlighting that targeting the RAB22A/PKM2/pSNAP axis is a potential novel strategy to reverse chemoresistance, and suggest circulating exosomal RAB22A and PKM2 as markers to predict the efficacy of chemotherapy in CRC. - Source: PubMed
Publication date: 2025/09/16
Yin YuanMing LiangQin YanTang JunhuiLiu BingxinLiu YuhangJin GuoyingJiang LingzhenYao SuruiQi XiaoweiHuang Zhaohui - Colorectal cancer metastasis remains a major cause of cancer-related mortality, with the Metastasis-Associated in Colon Cancer 1 (MACC1) protein emerging as a critical regulator of tumor progression. Although exosomes are recognized mediators of oncogenic communication, the interplay between MACC1 and exosome biology is yet to be fully explored. This study unveils a dual mechanism through which MACC1 coordinates exosome biogenesis and oncogenic cargo delivery to drive metastatic progression. We first established clinical relevance by Pearson's demonstrating a significant correlation between MACC1 expression and exosome concentration in colorectal tumors (r = 0.457, P < 0.05). Functional studies showed that MACC1-overexpressing HCT116 cells exhibited enhanced invasiveness and transmitted pro-metastatic signals via exosomes. These exosomes were significantly enriched in the c-Met oncoprotein (P < 0.05 vs. controls) and could induce epithelial-mesenchymal transition in recipient SW480 cells, significantly enhancing their migration and invasion capacities. Mechanistically, transcriptomic analysis identified several components of the exosome secretion machinery (YKT6, RAB22A, and VPS41) as downstream targets of MACC1. Promoter-binding assays confirmed that MACC1 directly activates the transcription of YKT6, a member of the Soluble N-ethylmaleimide-sensitive factor attachment protein receptor family. This protein is critical for multivesicular body-plasma membrane fusion. The transcriptional activation led to cytoplasmic accumulation of YKT6 (P < 0.05), driving a 2.9-fold increase in exosome secretion. Crucially, YKT6-mediated exosome hypersecretion facilitated the extracellular release of c-Met-enriched vesicles, establishing a feed-forward loop for metastatic propagation. Our findings delineate an integrated metastatic axis: MACC1 orchestrates (1) transcriptional upregulation of YKT6 to amplify exosome production, and (2) selective packaging of c-Met into exosomes that prime recipient cells for invasion. This dual regulatory mechanism highlights potential therapeutic targets for intercepting metastasis-specific exosome signaling in colorectal cancer. - Source: PubMed
Publication date: 2025/08/18
Hou ShenghuaiWang LingxiaoYang ChongLi YaopingLiu Haiyi