Ask about this productRelated genes to: WDR40A antibody
- Gene:
- DCAF12 NIH gene
- Name:
- DDB1 and CUL4 associated factor 12
- Previous symbol:
- KIAA1892, WDR40A
- Synonyms:
- DKFZP434O125, MGC1058, CT102, TCC52
- Chromosome:
- 9p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-11-21
- Date modifiied:
- 2016-10-05
Related products to: WDR40A antibody
Related articles to: WDR40A antibody
- Health conditions associated with rapid ascent to high altitudes remain prevalent and pose an ongoing challenge. While acute mountain sickness (AMS) typically occurs within the first few days after ascent, the physiological and molecular acclimatization processes during prolonged high-altitude exposure beyond the initial acute phase remain incompletely understood. - Source: PubMed
Publication date: 2026/02/18
Chen LingHe XuefeiWang HaoHu SihuZhao HaitongNi GuohuaYan HuiChen LeiDeng ChengLuo Fengming - Metastasis, the leading cause of cancer-related mortality, poses a fundamental proteostatic challenge, requiring rapid and precise proteome remodeling in response to stress. While ubiquitination is linked to protein degradation, our recent work uncovered a non-canonical, metastasis-promoting mechanism centered on DCAF12, a substrate receptor of the Cullin 4-RING ubiquitin ligase complex. DCAF12 mediates non-degradative ubiquitination of TRiC/CCT chaperonin subunits, allosterically activating the chaperonin to enhance its assembly, stability, and folding capacity. This ubiquitination-dependent activation circuit enables metastatic cells to efficiently fold and stabilize diverse pro-metastatic proteins, thereby facilitating dynamic proteome reprogramming. Herein, we present the DCAF12-TRiC/CCT axis as a central regulatory component of this adaptive response, explore its evolutionary basis, and propose DCAF12 as a prototype for a broader class of "DCAFome" regulators of chaperone function. This mechanistic understanding establishes a direct rationale for therapeutically targeting this axis to disrupt adaptive proteostasis. Moreover, we outline a therapeutic paradigm termed "proteostatic stress creation." This framework encompasses a spectrum of strategies, from precision protein-protein interaction inhibitors to state-selective degraders of DCAF12 or its ubiquitinated chaperonin subunits. These approaches can potentially disrupt the DCAF12-TRiC/CCT axis, thereby undermining the proteostatic resilience that sustains advanced cancers. - Source: PubMed
Publication date: 2026/01/20
Wei DongpingChen JiayanXu Yaping - The minichromosome maintenance (MCM2-7) protein complexes are central drivers of genome duplication. Distinct protein pools, parental and nascent MCMs, and their precise equilibrium are essential to sustain error-free DNA replication. However, the mechanism responsible for generating these pools and maintaining their equilibrium remains largely unexplored. Here, we identified CRL4 as a factor controlling the assembly of nascent MCM complexes. During MCM biogenesis, MCMBP facilitates the assembly and transport of newly synthesized MCM3-7 subcomplexes into the nucleus. Once in the nucleus, the MCM2 subunit must be incorporated into the MCM3-7 subcomplex, while MCMBP needs to be removed. CRL4 facilitates the degradation of MCMBP and thereby regulates the assembly of MCM2-7 complexes. The absence of CRL4 adversely affects the level of chromatin-bound nascent MCMs, resulting in accelerated replication forks and replication stress. Collectively, our findings uncovered the molecular mechanism underlying nascent MCM production essential to counteract genome instability. - Source: PubMed
Publication date: 2025/10/27
Yadav Anoop KumarAbdirov AlikhanOndruskova KatarinaNegi SimranJamrichova KristinaKolarova KarolinaDibus NikolKrejci JanaPolasek-Sedlackova HanaCermak Lukas - The transcriptional coactivator YAP1 regulates numerous biological processes, including organ size control and tissue homeostasis. Although its hyperactivity promotes tumor development and progression, YAP1 itself is not yet druggable. Here, we found that the poly(ADP-ribose) polymerase PARP1 promoted the transcriptional activity of YAP1-TEAD4 complexes that mediate breast cancer cell stemness, metastatic behavior, and evasion of antitumor immunity. This PARP1-mediated mechanism was independent of its role in the DNA damage response. Specifically, PARP1 directly interacted with and promoted the formation of the YAP1-TEAD4 complex by PARylating TEAD4 at a conserved Arg-Lys sequence. This PARP1-enhanced YAP1-TEAD4 binding attenuated the interaction between YAP1 and the E3 ubiquitin ligase CRL4, thus preventing its ubiquitylation and degradation. Furthermore, the abundance of PARP1 protein correlated with that of YAP1 and the immune checkpoint protein PD-L1 in breast cancer tissues and cell lines. In a mouse model of triple-negative breast cancer, pharmacological inhibition of PARP1 enhanced the ability of antibody blockade of PD-L1 to increase cytolytic and tumor-suppressive T cell infiltration and reduce tumor growth. The findings reveal a mechanism that promotes YAP1-TEAD4 transcriptional activity and immune escape in breast cancer cells and is targetable with clinically approved therapies. - Source: PubMed
Publication date: 2025/10/21
Guo YiboSong GaoqingZou HailinLu LiangxinDai XuyinSun ChuannanChen HaomingTong TongyuHuang MengjunZhu MengyuanDeng LiangHe YulongZhang ChanghuaLuo JuanLi Peng - Metastasis is the primary challenge in lung cancer treatment. Although proteostasis supports tumor growth, the mechanism by which ubiquitin ligases reprogram chaperone networks to drive metastasis is poorly understood. In this study, it is revealed that DDB1-CUL4-associated factor (DCAF12), a substrate receptor for CUL4-RING ubiquitin ligases, regulates metastatic progression through ubiquitin-mediated proteostatic reprogramming. DCAF12 depletion suppresses tumor cell migration and stemness in vitro and reduces pulmonary/hepatic metastasis in vivo. Mechanistically, DCAF12 catalyzes the non-degradative ubiquitination of TRiC/CCT subunits, enhancing chaperonin assembly and folding of cytoskeletal effectors (β-actin/tubulin) and oncogenic clients (STAT3/Raptor/mLST8), thereby activating the YAP, STAT3, and mTOR pathways. Both genetic knockdown and pharmacological blockade (via HSF1A) of this axis potently inhibit metastasis. Clinically, DCAF12 overexpression is correlated with YAP/STAT3 activation, advanced metastasis, and poor survival. Three key insights are revealed: 1) ubiquitination-mediated TRiC/CCT regulation as a metastatic switch, 2) DCAF12 as an oncogenic proteostasis hub, and 3) therapeutic potential validated through multimodal targeting. These findings establish the DCAF12-TRiC/CCT axis as a mechanistically novel target that simultaneously disrupts cytoskeletal dynamics and oncogenic signaling, making it a promising therapeutic strategy for metastatic lung cancer. - Source: PubMed
Publication date: 2025/10/05
Wang ZhenyiHuang HuanhuanHuang KaizongCui XiaowenWu LeileiLin RenyuZhao ZheChen HuaZheng ChengJin WeilinChen SongChen JiayanXu YapingWei Dongping