PRMT1 promotes the proliferation and metastasis of gastric cancer cells by recruiting MLXIP for the transcriptional activation of the ß-catenin pathway.

Protein arginine methyltransferase 1 (PRMT1), a type I PRMT, is overexpressed in gastric cancer (GC) cells. To elucidate the function of PRMT1 in GC, PRMT1 expression in HGC-27 and MKN-45 cells was knocked down by short hairpin RNA (shRNA) or inhibited by PRMT1 inhibitors (AMI-1 or DCLX069), which resulted in inhibition of GC cell proliferation, migration, invasion, and tumorigenesis in vitro and in vivo. MLX-interacting protein (MLXIP) and Kinectin 1 (KTN1) were identified as PRMT1-binding proteins. PRMT1 recruited MLXIP to the promoter of ß-catenin, which induced ß-catenin transcription and activated the ß-catenin signaling pathway, promoting GC cell migration and metastasis. Furthermore, KTN1 inhibited the K48-linked ubiquitination of PRMT1 by decreasing the interaction between TRIM48 and PRMT1. Collectively, our findings reveal a mechanism by which PRMT1 promotes cell proliferation and metastasis mediated by the ß-catenin signaling pathway.

Bombyx mori U-shaped regulates the melanization cascade and immune response via binding with the Lozenge protein.

Zinc finger protein, an important transcription factor, regulates gene expression associated with various physiological and pathological processes. U-shaped, belong to the Friend of GATA (FOG) transcription factor, plays a crucial role in hematopoiesis by interacting with the GATA transcription factor as a co-factor. However, little is known about its functions in insects. In the present study, a U-shaped cDNA was identified and characterized from the silkworm Bombyx mori and its potential roles in innate immunity investigated. The predicted silkworm U-shaped amino acid sequence contained a classical nuclear localization signal (NLS) motif "GESSPKRRRR" at position 450-459, and arginine residues at position 456 and 478 are the critical sites of the NLS. U-shaped mRNA was detected in all tested tissues of the B. mori; however, the highest levels were found in the hemocytes. U-shaped mRNA expression levels were upregulated in the hemocyte after the Escherichia coli and Staphylococcus aureus challenge. Furthermore, U-shaped knockdown significantly reduced the melanization process and suppressed the expression of melanization-associated genes, including PPO1, PPO2, PPAE and BAEE. In addition, U-shaped interacts with Lozenge protein to regulate the innate immune response of the insect. Our results revealed that U-shaped binds directly to Lozenge protein to modulate the melanization process and innate immune responses in silkworm.

Nup54-induced CARM1 nuclear importation promotes gastric cancer cell proliferation and tumorigenesis through transcriptional activation and methylation of Notch2.

Gastric cancer (GC) has the fifth highest incidence globally, but its molecular mechanisms are not well understood. Here, we report that coactivator-associated arginine methyltransferase 1 (CARM1) is specifically highly expressed in gastric cancer and that its overexpression correlates with poor prognosis in patients with gastric cancer. Nucleoporin 54 (Nup54) was identified as a CARM1-interacting protein that promoted CARM1 nuclear importation. In the nucleus, CARM1 cooperates with transcriptional factor EB (TFEB) to activate Notch2 transcription by inducing H3R17me2 of the Notch2 promoter but not H3R26me2. Additionally, the Notch2 intracellular domain (N2ICD) was identified as a CARM1 substrate. Methylation of N2ICD at R1786, R1838, and R2047 by CARM1 enhanced the binding between N2ICD and mastermind-like protein 1 (MAML1) and increased gastric cancer cell proliferation in vitro and tumor formation in vivo. Our findings reveal a molecular mechanism linking CARM1-mediated transcriptional activation of the Notch2 signaling pathway to Notch2 methylation in gastric cancer progression.