Ask about this productRelated genes to: OTUD6B Blocking Peptide
- Gene:
- OTUD6B NIH gene
- Name:
- OTU domain containing 6B
- Previous symbol:
- -
- Synonyms:
- CGI-77, DUBA5
- Chromosome:
- 8q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 2005-09-28
- Date modifiied:
- 2014-11-18
Related products to: OTUD6B Blocking Peptide
Related articles to: OTUD6B Blocking Peptide
- - Source: PubMed
Publication date: 2026/05/19
Yang DianLiu YichaoHong YueshunMiao EnmingWang PengSun YumingZhou LinaLiu ShuyanZhang YingqiuQin HongqiangYe MingliangLiu Han - The mechanism underlying acute pancreatitis (AP) is not fully understood. And the effect of s-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) in AP is unknown. - Source: PubMed
Publication date: 2026/05/09
Xiao JuanLi WanlianPan JianYang YinhuiChen Ji-AoLong Xi-Dai - Hepatocellular carcinoma (HCC) treatment faces dual challenges: resistance to targeted therapy and low response rates to immunotherapy. These issues are rooted in the immunosuppressive tumor microenvironment (TME). Ferroptosis and autophagy, two critical cellular processes, play complex and paradoxical roles in HCC drug resistance and immunoregulation, and they interact closely. This review explores how the OTU deubiquitinase family, especially OTUB1, acts as a central hub coordinating the autophagy-ferroptosis balance. Additionally, other OTU family members, such as OTUD3, OTULIN, and OTUD6B, contribute to HCC progression by modulating similar pathways, highlighting the need for a broader therapeutic approach. Specifically, OTUD3 suppresses HIF-1α-driven angiogenesis, OTULIN inhibits NF-κB-mediated inflammation, and OTUD6B stabilizes pVHL to impede metastasis, collectively demonstrating their synergistic or antagonistic interactions with OTUB1 in reshaping the TME. This coordination drives HCC drug resistance and remodels the immune microenvironment. OTUB1 suppresses ferroptosis and maintains tumor cell survival by deubiquitinating and stabilizing key proteins like SLC7A11, GPX4, and p62. It also promotes immune escape by modulating PD-L1 stability and immune cell function. Consequently, therapeutic strategies targeting the OTU family-such as developing selective inhibitors for multiple members, using intelligent nanodelivery systems, and combining them with ferroptosis inducers or immune checkpoint inhibitors-show significant potential for reversing drug resistance and improving immunotherapy efficacy. Expanding these strategies to include other OTU members could enhance efficacy and reduce resistance. Addressing how the OTU family precisely modulates the intersection of autophagy and ferroptosis, and how it reshapes immune cell metabolism and function within the TME, is critical for developing novel combination therapies. This article provides a crucial theoretical foundation for developing novel combination strategies targeting metabolism-immune crosstalk. - Source: PubMed
Publication date: 2026/05/05
Zhao PengchengZhang Ping - Liver metastasis remains a major cause of mortality in patients with colorectal cancer (CRC). Here, we identify OTUD6B, a deubiquitinating enzyme of the OTU family, as a key driver of CRC liver metastasis. OTUD6B is upregulated in metastatic CRC tissues and is correlated with poor prognosis. Functionally, OTUD6B promotes CRC cell proliferation, migration, and invasion in vitro and enhances tumor growth and liver metastasis in vivo. Mechanistically, OTUD6B binds the KH domain of fragile X-related protein 1 (FXR1) via its N-terminal region and stabilizes FXR1 by removing K48-linked polyubiquitin chains in a catalytic activity-dependent manner. In turn, FXR1 binds and stabilizes MEK2 mRNA, leading to increased MEK2 expression and activation of ERK signaling. Notably, FXR1 also upregulates OTUD6B expression, establishing a feed-forward loop that amplifies the oncogenic OTUD6B-FXR1-MEK2/ERK axis. OTUD6B, FXR1, and MEK2 levels are positively correlated in clinical CRC liver metastasis samples. Crucially, the MEK2 inhibitor U0126 acts synergistically with OTUD6B silencing to suppress liver metastasis. Collectively, these findings delineate a previously unrecognized oncogenic cascade in which OTUD6B stabilizes FXR1 to activate MEK2/ERK signaling, thereby driving CRC liver metastasis. Dual targeting of OTUD6B and MEK2 may represent a promising therapeutic strategy for advanced CRC. - Source: PubMed
Publication date: 2026/04/29
Lu YingLiu JiLi Ya-NanXiang LinSong Guo-BinPeng TianWang ZhenYang XueYing Hou-QunCheng Xue-Xin - Endometritis, a major inflammatory cause of infertility, is driven by unresolved immune dysregulation in which macrophage polarization is critical. Yet, how inflammatory signaling is spatially propagated within the endometrial microenvironment remains unclear. Here, we report that exosomes-natural nanoscale extracellular vesicles-released from lipopolysaccharide (LPS)-injured endometrial epithelial cells (EECs) act as pathogenic nanocarriers that fuel macrophage-dependent inflammation. We demonstrate that LPS enhances exosome biogenesis and secretion via the AKT/ATG16L1 pathway. These exosomes efficiently deliver their molecular cargo to macrophages, triggering NF-κB activation and polarizing them toward a pro-inflammatory M1 phenotype. RNA sequencing identified lncRNA OTUD6B-AS1 as a highly enriched cargo in exosomes from inflamed EECs. Functional studies established that exosome-mediated transfer of lncRNA OTUD6B-AS1 is both necessary and sufficient to drive M1 polarization. Mechanistically, lncRNA OTUD6B-AS1 functions as a competing endogenous RNA (ceRNA), sequestering miR-128 to relieve its repression on Notch2, thereby amplifying NF-κB signaling. This axis was validated in clinical endometritis tissues, which exhibited elevated lncRNA OTUD6B-AS1 and Notch2 alongside reduced miR-128. Importantly, targeting this pathway-through genetic knockdown of lncRNA OTUD6B-AS1 or pharmacological inhibition of the miR-128/Notch2 node-abolished the pro-inflammatory effects. Our work not only delineates a new exosome-coordinated signaling circuit in endometritis but also highlights exosomes as druggable natural nanoparticles. These findings position exosome-based engineering-such as cargo modulation or designed vesicle delivery-as a promising nanomedicine strategy to intercept pathological cell-cell communication and treat inflammatory diseases. - Source: PubMed
Publication date: 2026/03/14
Yang JingChen YajingWang KuiMi LifangChen YushanLi XiaobingYin GefenJiang Kangfeng