CBLL1

Last update 08 May 2025

Basic Info

Synonyms

c-Cbl-like protein 1, Casitas B-lineage lymphoma-transforming sequence-like protein 1, Cbl proto-oncogene like 1

+ [7]

Introduction

E3 ubiquitin-protein ligase that mediates ubiquitination of several tyrosine-phosphorylated Src substrates, including CDH1, CTTN and DOK1 (By similarity). Targets CDH1 for endocytosis and degradation (By similarity). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Its function in the WMM complex is unknown (PubMed:29507755).

100 Clinical Results associated with CBLL1

100 Translational Medicine associated with CBLL1

0 Patents (Medical) associated with CBLL1

114

Literatures (Medical) associated with CBLL1

01 Dec 2025·Genes & Nutrition

Decomposed interaction testing improves detection of genetic modifiers of the relationship of dietary omega-3 fatty acid intake and its plasma biomarkers with hsCRP in the UK Biobank

Article

Author: Meigs, James B ; Chasman, Daniel I ; Westerman, Kenneth E ; Patel, Chirag J ; Manning, Alisa K

Discovery and translation of gene-environment interactions (GxEs) influencing clinical outcomes is limited by low statistical power and poor mechanistic understanding. Molecular omics data may help address these limitations, but their incorporation into GxE testing requires principled analytic approaches. We focused on genetic modification of the established mechanistic link between dietary long-chain omega-3 fatty acid (dN3FA) intake, plasma N3FA (pN3FA), and chronic inflammation as measured by high sensitivity CRP (hsCRP). We considered an approach that decomposes the overall genetic effect modification into components upstream and downstream of a molecular mediator to increase the potential to discover gene-N3FA interactions. Simulations demonstrated improved power of the upstream and downstream tests compared to the standard approach when the molecular mediator for many biologically plausible scenarios. The approach was applied in the UK Biobank (N = 188,700) with regression models that used measures of dN3FA (based on fish and fish oil intake), pN3FA (% of total fatty acids measured by nuclear magnetic resonance), and hsCRP. Mediation analysis showed that pN3FA fully mediated the dN3FA-hsCRP main effect relationship. Next, we separately tested modification of the dN3FA-hsCRP ("standard"), dN3FA-pN3FA ("upstream"), and pN3FA-hsCRP ("downstream") associations. The known FADS1-3 locus variant rs174535 reached p = 1.6 × 10^-12 in the upstream discovery analysis, with no signal in the downstream analysis (p = 0.94). It would not have been prioritized based on a naïve analysis with dN3FA exposure and hsCRP outcome (p = 0.097), indicating the value of the decomposition approach. Gene-level enrichment testing of the genome-wide results further prioritized two genes from the downstream analysis, CBLL1 and MICA, with links to immune cell counts and function. In summary, a molecular mediator-focused interaction testing approach enhanced statistical power to identify GxEs while homing in on relevant sub-components of the dN3FA-hsCRP pathway.

26 Mar 2025·Open Medicine

Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development

Article

Author: Aziz, Tariq ; Al-Hoshani, Nawal ; Mughal, Muhammad Saad ; Alwethaynani, Maher S. ; Al-Joufi, Fakhria A. ; Naveed, Muhammad ; Tahir Kassim, Roaa Mohammed ; Ali Khan, Ayaz ; Makhdoom, Syeda Izma ; Jamil, Hamza

AbstractBackgroundColorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, emphasizing the need for improved prognostic biomarkers. Recent studies have identified the mRNA-modifying METTL3 oncogene as a potential biomarker in CRC progression.ObjectiveThis study aimed to investigate the expression patterns of METTL3 in CRC, assess its association with clinical outcomes, identify interacting proteins and biological pathways, and explore its correlation with immune cell infiltration.MethodsComprehensive analyses were conducted using public datasets, including transcriptome profiles from The Cancer Genome Atlas and the GSE103512 dataset. Protein–protein interaction (PPI) networks, pathway enrichment, and immune infiltration analyses were performed to elucidate METTL3’s role in CRC progression.ResultsMETTL3 expression was significantly higher in CRC tissues compared to normal tissues (p < 0.001). Mutations in METTL3 were detected in approximately 6% of CRC cases, with fusion events involving the SRPK2 gene. PPI analysis identified ten interacting proteins, including METTL4, EIF3H, RBM15B1, CBLL1, WTAP, NCBP1, RBM15, ZC3H13, METTL14, and KIAA1429. METTL3 expression showed a positive correlation with METTL4, METTL14, NCBP1, and WTAP expression (R > 0.5, p < 0.001). Higher METTL3 expression was associated with immunosuppressive phenotypes, such as increased infiltration of tumor-associated macrophages, regulatory T cells, and cancer-associated fibroblasts (p < 0.001). Pathway enrichment analysis revealed METTL3’s involvement in crucial pathways, including the cell cycle and renal cell carcinoma (p < 0.01). Gene ontology analysis highlighted its role in mRNA and RNA-related processes.ConclusionThe study supports the potential of METTL3 as a prognostic biomarker in CRC and highlights its involvement in immune modulation and cancer progression. These findings lay the groundwork for future studies aimed at developing targeted therapies and improving patient outcomes.

01 Mar 2025·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Steroid sulfatase suppresses keratinization by inducing proteasomal degradation of E-cadherin via Hakai regulation

Article

Author: Chun, Young-Jin ; Kwon, Yeo-Jung ; Park, Hyemin ; Kwon, Tae-Uk ; Kang, Keon Wook ; Lee, Hyein ; Kwak, Ji-Heung

X-linked ichthyosis (XLI) is a genetic disorder characterized by a steroid sulfatase (STS) deficiency inducing excessive cholesterol sulfate accumulation and keratinization. Our study utilizes STS knockout mice to reproduce the hyperkeratinization typical of XLI, providing a valuable model for investigating the underlying mechanisms. From the experiment of STS-deficient keratinocytes using the CRISPR/Cas9 system, we observed upregulation of E-cadherin, which is associated with keratinocyte differentiation and stratification. This was accompanied by elevated levels of keratinization markers, including involucrin and loricrin. We also found an increased expression of SULT2B1, which converts cholesterol to cholesterol sulfate, further accelerating cholesterol sulfate accumulation. As a result, STS deficiency and cholesterol sulfate accumulation lead to decreased expression of Hakai, the ubiquitin E3 ligase for E-cadherin. With reduced Hakai, endocytosis and ubiquitin-mediated degradation of E-cadherin are inhibited, resulting in its stabilization. This stabilization of E-cadherin is accompanied by increased expression of involucrin and loricrin, which is suppressed when the N-terminal extracellular domain of E-cadherin, responsible for cell-cell adhesion, is genetically modified. We propose that inhibition of E-cadherin, genetic modification of the N-terminal extracellular domain, and treatment with miR-6766 targeting E-cadherin significantly reduce the expression of keratinization markers, suggesting a potential therapeutic approach. We further suggest that the increased expression of E-cadherin observed in keratinocytes with STS deficiency is regulated by Hakai, underscoring the central role of E-cadherin in the pathogenesis of XLI.

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CBLL1

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