Ask about this productRelated genes to: HCC1 protein
- Gene:
- RBM39 NIH gene
- Name:
- RNA binding motif protein 39
- Previous symbol:
- RNPC2
- Synonyms:
- CC1.3, HCC1, CAPER, fSAP59, CAPERalpha
- Chromosome:
- 20q11.22
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-21
- Date modifiied:
- 2014-11-19
Related products to: HCC1 protein
Related articles to: HCC1 protein
- Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by immune dysregulation and pulmonary vascular remodeling. This study aimed to identify immune-associated hub genes in PAH using an integrative bioinformatics framework and to validate key candidates in an experimental model. - Source: PubMed
Publication date: 2026/05/22
Yang XitongZhou BinYang YingDong YuFu JifenLiu HongWu Xinhua - In recent years, the concept of "modality" has attracted significant attention in drug discovery, encompassing diverse approaches such as small molecules, antibodies, nucleic acids, and cell-based therapies. Eisai has leveraged its long-standing expertise in small-molecule drug design to focus on proximity-inducing compound (PIC), which induces novel pharmacological effects by bringing two distinct proteins into close proximity. PIC form ternary complexes between a target protein and an effector protein, enabling mechanisms such as targeted degradation, post-translational modification, and modulation of protein-protein interactions. This strategy allows intervention in previously "undruggable" targets that lack suitable binding pockets for conventional inhibitors. Among PIC, targeted protein degraders such as proteolysis targeting chimera (PROTAC) and molecular glue degrader (MGD) have advanced rapidly into clinical development worldwide. Eisai's entry into this field was driven by the discovery of the unique mechanism of action of Indisulam and E7820, which function as MGD to degrade RBM39 via DCAF15 recruitment. Building on this foundation, Eisai is pursuing tumor-selective strategies, including the development of a CEACAM6-targeted degrader antibody conjugate (DAC) and PROTAC utilizing tumor-selective E3 ligases. These approaches aim to achieve both efficacy and safety by restricting degradation activity to cancer cells. PIC represent a transformative modality that expands the druggable proteome and offers new therapeutic options for intractable diseases. This article outlines Eisai's efforts in PIC-based drug discovery, with a focus on targeted protein degradation and future perspectives. - Source: PubMed
Kira Kazunobu - Depletion of the splicing factor RBM39 disrupts spliceosome function and induces widespread RNA splicing defects, leading to antiproliferative effects in susceptible cancer cells. Here, we report the discovery and characterization of a new series of biphenyl-containing RBM39 degraders. The lead compound 42 promotes RBM39 degradation through formation of a ternary complex with RBM39 and DCAF15/DDB1 in a Cullin-RING E3 ligase- and proteasome-dependent manner, consistent with a molecular glue mechanism. Transcriptomic analyses in HCT-116 and K562 cells revealed extensive alternative splicing alterations and suppression of cell-cycle-associated pathways, resulting in G2/M-phase arrest without apoptosis. Comparative cellular profiling identified 41 (YSA64) as a potent analog in acute myeloid leukemia MV4-11 cells and Ewing sarcoma A673 cells, disease contexts that have been minimally explored for RBM39 degraders. Notably, 41 exhibited favorable oral pharmacokinetics and significant antitumor efficacy in MV4-11 xenograft models. Collectively, this work expands the chemical space of RBM39 degraders and supports their continued development as RNA splicing-targeted anticancer agents. - Source: PubMed
Publication date: 2026/05/02
Lyu XilinWang ZhiyiShen YanyanWang XianchengWang YixuanYu ShumengYang BiyuYan ZiqinZhang ShijieLu YuhangHuang HeChen YiZhao Yujun - Cigarette smoking significantly accelerates the initiation and progression of colorectal cancer (CRC), although the precise molecular mechanisms remain incompletely elucidated. Among tobacco-derived carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a key one, which has been demonstrated to enhance the malignant progression of CRC. CUT&RUN-seq and mRNA-seq analyses, along with subsequent validation experiments, reveal that NNK upregulates the expression of the acetyltransferase p300. This, in turn, mediates an increase in H3K27ac modification levels at the ANKHD1 promoter, thereby promoting ANKHD1 expression. Furthermore, high expression of ANKHD1 is significantly correlated with poor prognosis in CRC patients. Phenotypic experiments demonstrate that, compared to p300 overexpression alone, combined p300 overexpression with ANKHD1 knockdown partially suppresses the proliferation and metastatic capacity of CRC cells. This suggests that NNK may promote malignant CRC progression by upregulating the p300-ANKHD1 signaling axis. Further mechanistic investigations indicate that the scaffold protein ANKHD1 directly interacts with RBM39 to facilitate the splicing and expression of MKI67 pre-mRNA, thereby driving the malignant progression of NNK-exposed CRC cells. In summary, this study provides novel insights, proposing that targeting the p300-mediated H3K27ac modification pathway to suppress ANKHD1 expression may represent a promising therapeutic strategy and prognostic marker for CRC patients with a history of smoking. - Source: PubMed
Publication date: 2026/04/28
Jiang MinZhao YutingMa QunDing KunHuang YefeiChen Yansu - Cancer progression relies on dynamic post-transcriptional RNA regulation to enable phenotypic plasticity, immune evasion, and therapeutic resistance. RNA-binding motif (RBM) proteins emerge as pivotal orchestrators of these processes, modulating splicing, mRNA stability, and translation in a context-dependent manner across malignancies. This article provides a narrative mechanistic synthesis of published evidence and does not report original cohort construction or predictive-model development. Here, we review how RBM-driven RNA programs promote proliferative advantages through splicing rewiring, transcript stabilization via m6A modifications, and dual oncogenic/tumor-suppressive roles. We highlight RBM contributions to epithelial-mesenchymal transitions (EMT) and metastatic niche adaptation, including isoform-specific regulation of EMT effectors and metabolic reprogramming. Furthermore, RBMs shape tumor-immune dynamics by triggering innate immune activation through RNA misprocessing, suppressing adaptive immunity through PD-L1 upregulation, and remodeling the immunosuppressive microenvironment via cytokine and metabolic circuits. RBMs also integrate RNA processing with the choice of DNA repair pathways and genotoxic stress responses, underpinning resistance to chemotherapy and radiotherapy. Finally, pharmacological targeting of RBMs, such as RBM39 degradation via molecular glues like indisulam, exploits splicing dependencies to collapse oncogenic states and overcome resistance. These insights position RBMs as therapeutic nodes for precision immuno-oncology, with implications for biomarker-driven strategies in splicing-addicted tumors. - Source: PubMed
Publication date: 2026/04/13
Zhang JunLi YunfengHan HailingZhang Bingya