Ask about this productRelated genes to: SMC4 Blocking Peptide
- Gene:
- SMC4 NIH gene
- Name:
- structural maintenance of chromosomes 4
- Previous symbol:
- SMC4L1
- Synonyms:
- hCAP-C, CAP-C
- Chromosome:
- 3q25.33
- Locus Type:
- gene with protein product
- Date approved:
- 2001-02-22
- Date modifiied:
- 2016-10-05
Related products to: SMC4 Blocking Peptide
Related articles to: SMC4 Blocking Peptide
- Dosage compensation (DC) in C. elegans utilizes a condensin complex that resembles mitotic condensins, but differs by one subunit, DPY-27. DPY-27 replaces SMC-4, one of the Structural Maintenance of Chromosome (SMC) proteins that is responsible for hydrolyzing ATP, required for condensation of DNA and other mitotic condensin functions. To understand if the ATPase function is required in DC, we first demonstrated that DPY-27 is capable of hydrolyzing ATP in vitro. Then, we used CRISPR/Cas9-mediated genome editing to generate an ATPase mutation in dpy-27. Although the mutant protein is expressed and it is incorporated into the condensin IDC complex, this mutation results in a loss of DC. Specifically, we found that without ATPase function, DPY-27 containing condensin IDC has reduced capacity to bind DNA, condense the X chromosomes, and facilitate H4K20me1 enrichment on the X-chromosomes. Our results suggest that condensin IDC, like mitotic condensins, uses ATP hydrolysis to perform its functions, making C. elegans DC a model for how activities attributed to mitotic condensins can be used to regulate gene expression. - Source: PubMed
Publication date: 2026/03/17
Chawla BahaarJatia SuchiSloan DillonEduful JoshuaMendoza HectorMcClear Christian ATran JeannineCsankovszki Gyorgyi - Cervical cancer remains a significant global health burden, with the molecular determinants of its progression and therapeutic resistance not fully elucidated. This study aimed to identify DNA damage-related genes with prognostic and functional significance. - Source: PubMed
Publication date: 2026/03/09
Wu HaixiaYu YilinWang WeiXu Qin - Multiple myeloma (MM) is a complex hematological malignancy characterized by the uncontrolled proliferation of plasma cells in the bone marrow. Emerging evidence suggests that the aberrant activation of specific gene regulatory elements known as SE plays a crucial role in driving oncogenic gene expression programs in cancer. In this study, we investigated the role of the SE-driven SMC4 in promoting myeloma growth. Depletion of SMC4 resulted in a significant impairment of myeloma cell proliferation and clonogenicity. Mechanistically, we identified that SMC4 orchestrates the epigenetic modulation of the IFI16-dependent STING signaling pathway. This epigenetic enhancement of the IFI16-STING axis led to increased production of pro-inflammatory cytokines, creating a favorable microenvironment for myeloma cell growth. Furthermore, we established a direct link between the SE-driven SMC4 and the upregulation of IFI16 and STING gene expression in MM cells. Importantly, pharmacological inhibition of the IFI16-STING pathway abrogated the oncogenic effects mediated by SMC4. Our findings uncover a novel regulatory circuit involving SMC4 and the IFI16-STING signaling axis that promotes myeloma growth. Targeting this epigenetic network may hold therapeutic potential to intervene in myeloma progression and improve patient outcomes. - Source: PubMed
Publication date: 2026/03/07
Guan JiayunLin XuanyiDai ZhenfengZhou JianbiaoCai ZhenTan Tze KingChung Tae-HoonZhang XiaochenChng Wee-JooRong XiaoxiangJia Yunlu - Heat hormesis describes the beneficial adaptations resulting from transient exposure to mild heat stress, which enhances stress resilience and promotes healthy aging. While heat hormesis is widely observed, much remains to be learned about its molecular basis. This study bridges a critical knowledge gap through a comprehensive multiomic analysis, providing key insights into the transcriptomic and chromatin accessibility landscapes throughout a heat hormesis regimen in Caenorhabditis elegans. We uncover highly dynamic, dose-dependent molecular responses to heat stress and reveal that while most initial molecular changes induced by mild stress revert to baseline, key differences emerge in response to subsequent heat shock challenge that likely contribute to physiological benefits. We further demonstrate that heat hormesis extends life span specifically in wild-type animals, but not in germline-less mutants, likely due to transient disruption of germline activities during mild heat exposure, which appears sufficient to trigger pro-longevity mechanisms. This finding points to tissue-specific responses in mediating the physiological outcomes of heat hormesis. Importantly, we identify several highly conserved regulators of heat hormesis that likely orchestrate gene expression to enhance stress resilience. Among these regulators, some (MARS-1/MARS1, SNPC-4/SNAPc, FOS-1/c-Fos) are broadly required for heat-hormesis-induced benefits, whereas others (ELT-2/GATA4, DPY-27/SMC4) are uniquely important in specific genetic backgrounds. This study advances our understanding of stress resilience mechanisms, points to multiple new avenues for future investigations, and provides a molecular framework for promoting healthy aging through strategic mid-life stress management. - Source: PubMed
Publication date: 2026/02/20
Chang Hsin-YunMcMurry Sarah EMa SichengHeinke Charles LMansour Christian ASchwab Sophia Marie TDanko Charles GLee Siu Sylvia - Condensin, a structural maintenance of chromosomes (SMC) complex, plays a central role in genome organization by driving DNA loop extrusion through ATP hydrolysis. Experimental studies have revealed an asymmetric ATP-binding order at the Smc4- and Smc2-linked head domains, but the molecular origin and temperature dependence of this asymmetry remain poorly understood. Here, we combine coarse-grained switching-Gō models with all-atom molecular dynamics simulations to investigate how contact-network architecture in ATP-like states governs the order and thermal sensitivity of ATP-competent pocket formation. We find that the Smc4-associated ATP pocket (ATP1) exhibits higher local contact density and greater thermal stability than the Smc2-associated pocket (ATP2), favoring initial ATP1 pocket formation. As temperature increases, the formation of ATP2-binding-competent conformations becomes increasingly dependent on prior ATP1 pocket organization. Contact-network analysis of ATP-induced conformational transitions identifies specific structural regions that mediate this thermodynamic shift, revealing a temperature-dependent shift from independent to sequential pocket formation, consistent with the experimentally observed ATP-binding order at the two head sites. All-atom simulations provide supporting evidence that ATP1 pockets are highly persistent when the nucleotide is present but destabilize upon removal, whereas ATP2 pockets show greater intrinsic pre-organization in the ATP-absent state yet are less persistent when bound than ATP1 pockets. Together, these results advance a thermodynamic framework showing how contact-network connectivity encodes asymmetric, temperature-sensitive conformational competence for nucleotide engagement in condensin. - Source: PubMed
Xu ChengzhenChu Xiakun