Ask about this productRelated genes to: KLHL13 Blocking Peptide
- Gene:
- KLHL13 NIH gene
- Name:
- kelch like family member 13
- Previous symbol:
- BKLHD2, KIAA1309
- Synonyms:
- FLJ10262
- Chromosome:
- Xq24
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-23
- Date modifiied:
- 2016-10-05
Related products to: KLHL13 Blocking Peptide
Related articles to: KLHL13 Blocking Peptide
- Despite the accumulating evidence that diabetes and centrosome amplification (CA) are both associated with cancer cell metastasis, in particular the observations in gene-edited animal models, their relationships and the underlying molecular mechanisms remain unknown under pathophysiological conditions. In the present study, we examined if CA could serve as a biological link between diabetes and metastasis. Our results showed that, in vitro, advanced glycation end products (AGEs) promoted CA, migration, and invasion of HCT116 colorectal cancer cells, with the highest CA level in the migrated cell fraction, and upregulated FAM111B, which promoted epithelial-mesenchymal transition. Upon AGE treatment, Krüppel-like factor 5 (KLF5), Kelch-like (KLHL)13, and Cullin3 (CUL3) were downregulated and CEP57L1 was upregulated, respectively; the latter was due to an insufficient KLF5-mediated transcription of KLHL13 and CUL3 and therefore compromised protein ubiquitination degradation. Importantly, AGEs promoted CEP57L1-dependent metastasis of the cancer cells in a mouse model. In a cohort of cancer patients, KLF5, KLHL13, and CUL3 levels were lower, but CA and CEP57L1 were higher in cancer tissues, compared with noncancerous counterparts, which were more obvious in those with diabetes. Decreased KLF5, KLHL13, and CUL3, together, were associated with poorer survival. In conclusion, it is suggested that AGEs promote the cancer cell metastasis via CA by KLF5-CEP57L1 axis, which underlies diabetes-promoted cancer metastasis. - Source: PubMed
Publication date: 2025/12/22
Zhao Ji ZhongFan Sheng XianGuo Jia LiLu Yu ChengBian Xue KaiHan Ya WenXu Si XianZhao Meng LuLi Yuan FeiLi Rong PengLee Shao Chin - Although ubiquitin-conjugating enzymes are critical regulators of cellular function and fate, their roles in tumorigenesis remain incompletely defined. Here, we provide genetic and molecular evidence that the Ubiquitin-Conjugating Enzyme E2 D3 (UBE2D3) is specifically overexpressed in cancerous pancreatic ductal cells, including early-stage pancreatic intraepithelial neoplasia and advanced pancreatic ductal adenocarcinoma (PDAC). This overexpression is independent of oncogenic KRAS status and is driven by the inflammatory tumor microenvironment, particularly interferon-γ (IFN-γ). Mechanistically, UBE2D3 binds the ubiquitin ligase Kelch Like Family Member 13 (KLHL13) to mediate K63-linked polyubiquitination at lysine 245 of transporter 2 (TAP2), resulting in steric hindrance that blocks the transporter. Genetic or pharmacologic inhibition of UBE2D3 enhances antigen presentation in cancer cells and restores CD8 T-cell-mediated tumor surveillance in pancreatic cancer models in male mice. Furthermore, combining an UBE2D3 small-molecule inhibitor with KRAS-specific TCR-T-cell therapy yields synergistic antitumor effects. Our findings reveal a negative feedback mechanism in which cancer cells, "camouflaging" themselves, evade IFN-γ-induced antigen presentation via UBE2D3 upregulation, highlighting a potential therapeutic target for enhancing antitumor immunity. - Source: PubMed
Publication date: 2025/11/28
Wang ShiqunYang WenyanPeng TiZhu ChunxiaoDong JinyunWang YichaoYuan HuSun QingyanLuan XinGuan XiaoqingZhang WeidongQin Jiang-Jiang - Neurodevelopmental disorders (NDDs) are characterized by limitations in brain development. This study aims to determine the genetic causes of NDD in humans. - Source: PubMed
Publication date: 2025/10/25
Akhter TehmeenaAhmed Zubair MJi YapingSchmidt AxelAzage MeronPalomares MariaCremer KirstenEngels HartmutMurphy Jennifer OPeters SophiaMangold ElisabethGomez-Cano M L ÁTaylor Rodney JRiazuddin SheikhRiazuddin Saima - Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy associated with poor clinical outcomes. RHOBTB2, an atypical member of the Rho-GTPase family, contains a conserved GTPase domain at its N-terminus. While previous studies have implicated RHOBTB2 in AML progression, its underlying mechanisms remain inadequately defined. In this study, bioinformatics analyses revealed that RHOBTB2 is markedly upregulated in AML and correlates with unfavorable prognosis. To elucidate its functional role, we overexpressed or silenced RHOBTB2 in human AML cell lines KG-1 and MOLM-13. Functional assays, including CCK-8, Transwell, and Annexin V/PI staining, demonstrated that RHOBTB2 overexpression enhanced proliferation and migration, suppressed apoptosis, and shortened G0/G1 phase. Conversely, RHOBTB2 silencing exerted opposing effects. In addition, a direct interaction between RHOBTB2 and KLHL13 was identified through STRING database predictions and validated by co-immunoprecipitation. Western blot analysis confirmed that RHOBTB2 upregulates KLHL13 protein expression levels. Notably, KLHL13 downregulation induced by RHOBTB2 knockdown was reversed upon treatment with the proteasome inhibitor MG132, indicating that RHOBTB2 stabilizes KLHL13 by inhibiting its proteasomal degradation. Collectively, our findings highlight the RHOBTB2/KLHL13/Hippo pathway as a critical regulatory mechanism in AML malignancy and suggest RHOBTB2 as a potential therapeutic target. - Source: PubMed
Publication date: 2025/10/17
Liu YaoZhou FanghuiWang LianjieXue YanmingWang Wei - () is a facultative intracellular parasitic pathogen with multiple immune escape mechanisms. Mitophagy is critical for mitochondrial quality control and function in various biological processes. We reported that infection induces mitophagy to promote its intracellular survival by decreasing mitochondrial reactive oxygen species (mtROS). Mechanically, infection leads to the rupture of host outer mitochondrial membrane (OMM) by DNM1L/DRP1 (dynamin 1-like). Furthermore, BipD, the type III secretion system (T3SS) needle tip protein of , hijacks the host KLHL9 (kelch-like 9)-KLHL13 (kelch-like 13)-CUL3 (cullin 3) E3 ubiquitin ligase complex to promote the K63-linked ubiquitination of IMMT/mitofilin (inner membrane protein, mitochondrial) at the K211 site. Then BipD-initiated mitophagy, via the conventional macroautophagy/autophagy pathway with the receptor SQSTM1 (sequestosome 1) involvement, decreases the mtROS production, which in turn facilitates the intracellular survival of . Here, our findings reveal an unexpected function of BipD and the KLHL9-KLHL13-CUL3 E3 ligase complex and suggest a novel mechanism used by bacterial pathogens that hijack host mitophagy for their survival. - Source: PubMed
Publication date: 2024/09/18
Nan DongqiMao XuhuLi Qian