Ask about this productRelated genes to: CDKN2AIP antibody
- Gene:
- CDKN2AIP NIH gene
- Name:
- CDKN2A interacting protein
- Previous symbol:
- -
- Synonyms:
- FLJ20036, CARF
- Chromosome:
- 4q35.1
- Locus Type:
- gene with protein product
- Date approved:
- 2006-11-17
- Date modifiied:
- 2014-11-19
Related products to: CDKN2AIP antibody
Related articles to: CDKN2AIP antibody
- DNA is subjected to damage from various endogenous and exogenous sources of alkylating agents, resulting in alkylated DNA lesions. Among these lesions, -methyl-2'-deoxyguanosine (-Me-dG) is highly mutagenic, and it can be repaired by -alkylguanine DNA alkyltransferase and mismatch repair pathway. It, however, remains unclear whether -Me-dG in DNA can be recognized by other cellular proteins. Here, we employed a quantitative mass spectrometry-based approach to uncover reader proteins of -Me-dG in DNA when it is paired with a 2'-deoxycytidine (dC) or thymidine (dT). We were able to identify 67 and 31 candidate reader proteins for duplex DNA harboring -Me-dG:dC and -Me-dG:dT base pairs, respectively. In addition, genetic ablation of CDKN2AIP, a.k.a. CARF, one of those proteins that can recognize both the -Me-dG:dC and -Me-dG:dT base pairs, in HEK293T cells conferred augmented tolerance to -nitroso--methylurea (NMU), an alkylating agent that can induce -Me-dG in DNA. Accordingly, our LC-MS/MS quantification results revealed that the loss of CDKN2AIP led to diminished accumulation of NMU-induced -Me-dG in genomic DNA. Together, we explored the damage recognition proteins of -Me-dG using a quantitative mass spectrometry-based approach, and our results revealed an unexpected role of CDKN2AIP in sensitizing cultured cells toward a DNA methylating agent. - Source: PubMed
Publication date: 2025/07/17
Kellum Andrew HWang Michelle YZhao TingLiu XiaochuanHe XiaomeiLi LinWilliams PrestonZhang QuanqingWang Yinsheng - ADP-ribosylation factor collaborator (CARF), which is also known as CDKN2AIP, was first recognized as an ADP-ribosylation factor-interacting protein that participates in the activation of the ARF-p53-p21 (WAF1) signaling pathway under different conditions, such as oxidative and oncogenic stresses. The activation of this pathway often leads to cell growth arrest and apoptosis as well as senescence. Previous studies revealed that CARF, an RNA-binding protein, is critical for maintaining stem cell pluripotency and somatic differentiation. Nevertheless, its involvement in spermatogenesis has not been well examined. In this study, we show that male mice deficient in expression present impaired spermatogenesis and fertility. IP-MS and RNA-seq analyses reveal that CARF/ interacts with multiple key splicing factors, such as PABPC1, and directly targets 356 different types of mRNAs in spermatocytes. -associated mRNAs display aberrant splicing patterns when Carf expression is deficient. In addition, our results demonstrate that PIWIL1 expression and localization are altered in the mouse model through the downregulation of PABPC1, which further affects the ratio of pachytene-piRNA. Our study suggests that CARF is critical for regulating alternative splicing in mammalian spermatogenesis and determining infertility in male mice. - Source: PubMed
Cao YumingWang ShengnanLiu JieXu JinfengLiang YanAo FeiWei ZexiaoWang Li - Nuclear receptor subfamily 4 group A member 3 (NR4A3) is a member of the orphan nuclear receptor superfamily, and exhibits transcription factor activity by binding to sequence-specific DNA. Considering that the specific mechanism by which NR4A3 regulates gene transcription in HCC (hepatocellular carcinoma) has not yet been elucidated, our study aimed to explore the transcriptional role of NR4A3 in regulating the target gene CDKN2AIP (CDKN2A interacting protein), which will suppress the development of HCC. Our data show that NR4A3 is downregulated in human HCC tissues, and that low expression of NR4A3 is correlated with poor prognosis, indicating that NR4A3 could act as a tumor suppressor gene in HCC. NR4A3 overexpression suppresses cell proliferation, clone formation, cell cycle arrest at G0/G1 phase and tumor growth and and promote DNA damage. NR4A3 could directly regulate the expression of CDKN2AIP at the transcriptional level, suggesting that NR4A3 may play a role as a transcription factor in HCC and may serve as a potential biomarker for predicting prognosis for HCC patients. - Source: PubMed
Publication date: 2024/10/28
Zhao XingeMin XuejieWang ZhenyuChen XiaoxiaGe ChaoZhao FangyuTian HuaChen TaoyangLi Jinjun - We investigated the effect of purified withanolides and extracts derived from Ashwagandha on steatosis, the abnormal accumulation of fat that can lead to non-alcoholic fatty liver disease (NAFLD). Collaborator of ARF (CARF, also known as CDKN2AIP, a protein that regulates hepatic lipid metabolism, fat buildup, and liver damage) was used as an indicator. Six withanolides (Withaferin A, Withanone, Withanolide B, Withanoside IV, Withanoside V, and Withanostraminolide-12 deoxy) reversed the decrease in CARF caused by exposure to free fatty acids (FFAs) in liver-derived cells (HepG2 hepatocytes). After analyzing the effects of these withanolides on CARF mRNA and protein levels, FFA accumulation, protein aggregation, and oxidative and DNA damage stresses, we selected Withaferin A and Withanone for molecular analyses. Using the palmitic-acid-induced fatty acid accumulation stress model in Huh7 cells, we found a significant reduction in the activity of the key regulators of lipogenesis pathways, including sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FASN), and peroxisome proliferator-activated receptors (PPARγ and PPARα). This in vitro study suggests that low, non-toxic doses of Withaferin A, Withanone, or Ashwagandha extracts containing these withanolides possess anti-steatosis and antioxidative-stress properties. Further in vivo and clinical studies are required to investigate the therapeutic potential of these Ashwagandha-derived bioactive ingredients for NAFLD. - Source: PubMed
Publication date: 2024/11/14
Li DongyangHan HanlinSun YixinZhang HuayueYoshitomi RenKaul Sunil CWadhwa Renu - HNF4A and HNF1A encode transcription factors that are important for the development and function of the pancreas and liver. Mutations in both genes have been directly linked to Maturity Onset Diabetes of the Young (MODY) and type 2 diabetes (T2D) risk. To better define the pleiotropic gene regulatory roles of HNF4A and HNF1A, we generated a comprehensive genome-wide map of their binding targets in pancreatic and hepatic cells using ChIP-Seq. HNF4A was found to bind and regulate known (ACY3, HAAO, HNF1A, MAP3K11) and previously unidentified (ABCD3, CDKN2AIP, USH1C, VIL1) loci in a tissue-dependent manner. Functional follow-up highlighted a potential role for HAAO and USH1C as regulators of beta cell function. Unlike the loss-of-function HNF4A/MODY1 variant I271fs, the T2D-associated HNF4A variant (rs1800961) was found to activate AKAP1, GAD2 and HOPX gene expression, potentially due to changes in DNA-binding affinity. We also found HNF1A to bind to and regulate GPR39 expression in beta cells. Overall, our studies provide a rich resource for uncovering downstream molecular targets of HNF4A and HNF1A that may contribute to beta cell or hepatic cell (dys)function, and set up a framework for gene discovery and functional validation. - Source: PubMed
Publication date: 2024/06/22
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