Ask about this productRelated genes to: p21Cip1 antibody
- Gene:
- CDKN1A NIH gene
- Name:
- cyclin dependent kinase inhibitor 1A
- Previous symbol:
- CDKN1
- Synonyms:
- P21, CIP1, WAF1, SDI1, CAP20, p21CIP1, p21Cip1/Waf1, p21
- Chromosome:
- 6p21.2
- Locus Type:
- gene with protein product
- Date approved:
- 1994-05-24
- Date modifiied:
- 2018-06-06
Related products to: p21Cip1 antibody
Related articles to: p21Cip1 antibody
- Methotrexate (MTX) is the first-line treatment for rheumatoid arthritis (RA), but patient responses are highly variable. Macrophages are central drivers of RA inflammation, yet how monocyte/macrophage heterogeneity and transcriptional programs influence MTX responsiveness remains unclear. Single-cell RNA sequencing was performed on peripheral blood mononuclear cells from MTX-responsive and MTX-unresponsive RA patients to define immune composition and macrophage-like monocyte subsets. Polarization states were assessed using gene-signature scoring and pseudotime analysis. The role of inhibitor of differentiation 2 (ID2) was examined in LPS-stimulated RA patient-derived macrophages using gain- and loss-of-function approaches, cytokine assays and chromatin immunoprecipitation assays. Although overall immune cell distributions were similar between groups, macrophage-like monocytes from MTX-unresponsive patients exhibited higher M1 polarization scores. PLBD1⁺ and CDKN1A⁺ macrophage-like monocytes were enriched in MTX-unresponsive patients, whereas RLIM⁺ macrophage-like monocytes were reduced. Integrative analyses identified ID2 as a regulator associated with MTX resistance. ID2 expression was elevated in macrophage-like monocytes from MTX-unresponsive patients and positively correlated with M1 polarization. In vitro, MTX suppressed ID2 expression and inflammatory activation. ID2 knockdown reduced pro-inflammatory responses, whereas overexpression attenuated the inhibitory effects of MTX. ID2 was found to regulate EEF1A1 transcription. ID2 promotes pro-inflammatory macrophage polarization and may contribute to MTX resistance in RA. - Source: PubMed
Publication date: 2026/05/22
Ye LuWang XiaomeiWu HuaxiangXu Weihong - While venetoclax-based combinations have shown promising results in acute myeloid leukemia (AML), the remission duration is generally short, warranting strategies to further improve efficacy and overcome resistance. Here, we show that the natural quassinoid brusatol induces cell-cycle arrest and apoptosis in multiple AML cell lines while enhancing venetoclax efficacy irrespective of inherent or acquired resistance. Mechanistically, brusatol increased p53 protein expression, leading to upregulation of its target genes/proteins, including CDKN1A (p21) and BBC3 (PUMA). Genetic deletion of TP53 attenuated brusatol-induced apoptosis and its synergy with venetoclax, supporting p53 activation as a central mechanism underlying the anti-leukemia response. Furthermore, the combination synergistically decreased mitochondrial membrane potential and respiratory activity, causing accumulation of reactive oxygen species in AML cells. Although brusatol and venetoclax exhibited limited effects individually, their combination markedly reduced leukemia burden and significantly prolonged survival in three independent cell line-derived xenograft models, including venetoclax-resistant and -refractory models. Notably, brusatol increased normal leukocyte and platelet counts while reducing leukemic infiltration in both bone marrow and extramedullary sites. These findings provide mechanistic insight into the synergistic effects of the brusatol-venetoclax combination, supporting further evaluation of this therapeutic strategy in myeloid leukemias. - Source: PubMed
Publication date: 2026/05/21
Kawaguchi Shin-IchiroSato KazuyaIzawa JunkoTakayama NorihitoHayakawa HirokoSuzaki KenGoyama SusumuKato ChiyokoSakashita EijiTominaga KaoruEndo HitoshiKanda Yoshinobu - Point mutations in p53 favour tumour aggressivity, particularly in gastric cancer (GC), and offer a target for small molecule-based anticancer treatments. This study focused on the p53-Y220C mutation, which causes p53 misfolding due to thermal instability associated with the creation of a pocket that may accommodate small molecules. This mutation also creates an additional free cysteine thiol group that may react with Michael acceptors. Using an integrated and approach, four compounds (AG1, AG2, AG3, and RK349) were screened for potential reactivation of p53-Y220C in GC cells. AG3, a compound with zinc chelation and Michael acceptor properties, was found to induce p53 target gene expression via p53-dependent and -independent pathways. AG3 limited reactive oxygen species production, reducing toxicity to healthy cells. Furthermore, AG3 induced p53-dependent cytotoxicity and enhanced chemotherapy response. This study presents a novel compound with p53-Y220C reactivation potential, highlighting its promise for further development. - Source: PubMed
Publication date: 2026/05/21
Nannini SimonSieffert CélineMcGown AndrewGao Xin-YueJarvis AmandaKostakis Georges EGalvacsi AntalKallay CsillaMoraru RuxandraBaud Matthias GMandel SebastianBalourdas Dimitros-IliasJoerger Andreas COrvain ChristophePeschard SimonNion AudreyMellitzer GeorgLottiaux SophieSpencer JohnGross IsabelleGaiddon Christian - Class IIa histone deacetylase 7 (HDAC7) regulates transcription primarily through scaffolding functions, but its molecular mechanisms in cancer pathogenesis remain incompletely understood. Here, we establish HDAC7 as a key epigenetic regulator in colorectal cancer (CRC). HDAC7 is overexpressed in CRC tumors and correlates with advanced disease stages, lymph node metastasis, and poor patient survival. Mechanistically, HDAC7 scaffolds a repressive complex with HDAC3 and the stress-responsive transcription factor ATF3. This reduces H3K27ac/H3K18ac occupancy and blocks BRD4/RNA polymerase II (Pol II) recruitment at regulatory regions to epigenetically silence its transcription. Consequently, this repression inactivates ATF3's tumor-suppressive functions, activating oncogenic PI3K-Akt signaling while suppressing the Hippo pathway. Genetic depletion or pharmacological inhibition of HDAC7 disrupts this repressive complex, triggering a functional switch in ATF3. This promotes BRD4/Pol II recruitment and H3K27ac enrichment at the ATF3 locus, enabling ATF3 to undergo transcriptional self-activation. Reactivated ATF3 suppresses CRC proliferation and survival by downregulating Bcl-2, upregulating p21 () to induce cell cycle arrest, promoting caspase-3-mediated apoptosis, and inhibiting PI3K-Akt signaling. Xenograft studies confirm that HDAC7 depletion suppresses tumorigenicity . Our work identifies HDAC7 as a molecular mediator that governs ATF3's functional plasticity through competitive cofactor recruitment, positioning HDAC7 inhibition as a therapeutic strategy to reactivate ATF3-mediated tumor suppression in CRC. - Source: PubMed
Publication date: 2026/05/01
Wang QiJi DongleiJia YanjieLi ShuangGao WenjingLiang TingtingLiang YingyingZeng CarolineWang ChunyuCheung Ka LungWang QuanZhou Ming-MingZeng Lei - Prurigo nodularis (PN) is a chronic pruritic dermatosis with incompletely defined pathogenesis, and molecular data from East Asian populations are limited. We characterized the transcriptomic signatures of non-atopic PN in Korean patients to identify pathways linked to chronic itch and lesion persistence. RNA sequencing was performed on lesional and non-lesional skin from 17 PN patients and normal skin from 11 controls, followed by differential expression, functional enrichment, and correlation analyses. Lesional PN skin showed distinct transcriptional signatures with upregulation of Th22/IL-22-related genes and IL-22-inducible epidermal stress markers (S100A7/A8/A9, SERPINB4, HRNR), along with keratinization genes (KRT6C, KRT16, KRT17). Itch severity correlated strongly (Spearman's ρ>0.7) with IL-22-inducible stress genes, IL4R, profibrotic mediators (WNT5A), JAK-STAT regulators (JAK3, SOCS1/3), neuromodulatory/epidermal-neural genes (TRPV3), and senescence markers (CDKN1A, CXCL8, PLAUR). Non-lesional skin showed intermediate expression patterns, consistent with subclinical inflammation. Despite the modest sample size and single-ethnicity design, these findings indicate that non-atopic PN in Korean patients is characterized by IL-22-driven epidermal stress, fibroblast remodelling, neuroimmune signalling, and senescence programsprogrammes, highlighting therapeutic targets including IL-31RA, IL-4Rα/JAK1, antifibrotic and senescence-directed pathways. - Source: PubMed
Publication date: 2026/05/18
Kim Hei SungKim Yoon-SeobYosipovitch Gil