Ask about this productRelated genes to: HIPK4 Blocking Peptide
- Gene:
- HIPK4 NIH gene
- Name:
- homeodomain interacting protein kinase 4
- Previous symbol:
- -
- Synonyms:
- FLJ32818
- Chromosome:
- 19q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2004-01-29
- Date modifiied:
- 2014-11-19
Related products to: HIPK4 Blocking Peptide
Related articles to: HIPK4 Blocking Peptide
- Are pathogenic variants in () associated with sperm head abnormalities that cause male infertility? - Source: PubMed
Publication date: 2026/07/20
Koser Sophie AdinaRieck CynthiaAprea IsabellaKrallmann ClaudiaGaikwad Avinash SatishWallmeier JuliaTenardi-Wenge RetnoDi Persio SaraNeuhaus NinaRaidt JohannaOmran HeymutLaurentino SandraKliesch SabineStallmeyer BirgitFriedrich CorinnaTüttelmann Frank - Homeodomain-interacting protein kinase 4 (HIPK4) is a dual-specificity kinase that is predominantly expressed in differentiating spermatids, required for sperm development, and a promising target for nonhormonal male contraception. Genetic and functional studies have established an essential role for HIPK4 in spermiogenesis, where it acts at least in part through regulation of the F-actin-scaffolded acroplaxome during spermatid head shaping. The direct molecular targets of HIPK4 and their downstream effectors remain poorly defined, and small-molecule probes would be versatile tools for further investigating HIPK4 functions. Synthetic HIPK4 ligands could also be valuable leads for the development of nonhormonal male contraceptives. Here, we report the discovery of a cyanoquinoline-based series of HIPK4 inhibitors with nanomolar potency. Our lead compounds are selective for HIPK4, both within the HIPK family and across the broader kinome, establishing this scaffold as a useful starting point for probe and lead development. Unexpectedly, we found that a subset of these cyanoquinolines also perturbs HIPK4 proteostasis in a cell type-specific manner. In spermatids, these compounds induce the formation of detergent-insoluble HIPK4 aggregates and promote interactions between this kinase and the autophagy receptor Tax1-binding protein 1 (TAX1BP1). Together, our findings establish cyanoquinoline ligands as a new chemotype for probing HIPK4 biology and advancing male contraceptive discovery. - Source: PubMed
Publication date: 2026/05/14
Zhuang ZaileTogashi Riley KKearney PatrickPass IanSwick Steven MZeng Fu-YueBobkov Andrey AFujimoto Lynn MDutta ShubhankarZerva AthinaRaig Nicolai DSaha DebasmitaEmami AtoosaSchwalm Martin PMoon Bradley KHoward Samuel TKnapp StefanHanke ThomasChung Thomas D YChen James K - Homeodomain-interacting protein kinase 4 (HIPK4) remains an understudied member of the dark kinome. While genetic knockout studies suggest roles for HIPK4 in spermiogenesis and cutaneous squamous cell carcinoma, whether these cellular functions can be recapitulated by pharmacological inhibition remains to be determined. However, such investigations have been hampered by a lack of high-quality chemical tools. To address this, we employed a rational design strategy utilizing macrocyclization of a bosutinib-based scaffold. Systematic optimization led to the discovery of (), a potent and selective HIPK4 inhibitor (IC = 11 nM; cellular EC = 76 nM). exhibits exceptional selectivity across three comprehensive orthogonal panels, high solubility, and no detectable cytotoxicity. Its cellular activity was confirmed in cell-based assays of HIPK4-dependent F-actin remodeling. Together with a negative control compound, this probe set provides a foundational framework for the validating HIPK4 as a therapeutic target and a high-quality resource to elucidate its roles in normal physiology and disease. - Source: PubMed
Publication date: 2026/05/28
Zerva AthinaRaig Nicolai DZhuang ZaileKrämer AndreasDopfer JohannesTogashi RileySchwalm Martin PElson LewisFrischkorn Julia MBerger Benedict-TilmanMüller SusanneChen James KKnapp StefanHanke Thomas - Cutaneous squamous cell carcinoma (CSCC) is a common skin cancer with a tendency to metastasize, leading to poor patient prognosis. Homeodomain interacting protein kinase 4 (HIPK4) has been identified as a key inhibitor of human skin epithelial differentiation. However, the role of HIPK4 in regulating CSCC development remains unclear. Our preliminary experiment showed that HIPK4 was highly expressed in CSCC tumor tissues and cells. In this study, we investigate the role of HIPK4 in regulating CSCC progression and the underlying mechanisms. In the current study, the interaction between HIPK4 and TAp63 was analyzed by Co-IP and GST-pull down assays, and the relationship between TAp63 and EFEMP1 was analyzed by ChIP and dual luciferase reporter assays. Our results showed that EFEMP1 expression was decreased in CSCC tissues and cells, and EFEMP1 overexpression inhibited CSCC cell proliferation, migration, and invasion. In addition, HIPK4 was upregulated in CSCC; knocking down HIPK4 suppressed CSCC cell malignant behaviors and tumor growth in mice. Mechanistically, HIPK4 promoted tumor progression by phosphorylating the tumor suppressor TAp63 at Ser395, leading to decreased expression of EFEMP1, a key extracellular matrix protein with anti-tumor properties. As expected, the inhibitory effects of HIPK4 knockdown on CSCC cell malignant behaviors were reversed by EFEMP1 knockdown. In summary, HIPK4 could exacerbate CSCC malignant progression by inhibiting EFEMP1 through phosphorylating TAp63, highlighting HIPK4 as a potential therapeutic target in CSCC. Our results provide new insights into the molecular mechanisms underlying CSCC progression and propose novel strategies for therapeutic intervention. - Source: PubMed
Publication date: 2025/04/30
Guo ZeChen BingjieZhang MengyaGao MinWang ZaixingTang HuayangTang XianfaZhang QianUtikal Jochen - Indigenous pig populations in Hainan Province live in tropical climate conditions and a relatively closed geographical environment, which has contributed to the formation of some excellent characteristics, such as heat tolerance, strong disease resistance and excellent meat quality. Over the past few decades, the number of these pig populations has decreased sharply, largely due to a decrease in growth rate and poor lean meat percentage. For effective conservation of these genetic resources (such as heat tolerance, meat quality and disease resistance), the whole-genome sequencing data of 78 individuals from 3 native Chinese pig populations, including Wuzhishan (WZS), Tunchang (TC) and Dingan (DA), were obtained using a 150 bp paired-end platform, and 25 individuals from two foreign breeds, including Landrace (LR) and Large White (LW), were downloaded from a public database. A total of 28,384,282 SNPs were identified, of which 27,134,233 SNPs were identified in native Chinese pig populations. Both genetic diversity statistics and linkage disequilibrium (LD) analysis indicated that indigenous pig populations displayed high genetic diversity. The result of population structure implied the uniqueness of each native Chinese pig population. The selection signatures were detected between indigenous pig populations and foreign breeds by using the population differentiation index () method. A total of 359 candidate genes were identified, and some genes may affect characteristics such as immunity (, and ), adaptability (), reproduction (, , and ), meat quality (, , and ), and heat tolerance (, ). Overall, the findings of this study will provide some valuable insights for the future breeding, conservation and utilization of these three Chinese indigenous pig populations. - Source: PubMed
Publication date: 2023/06/16
Zhong ZiqiWang ZiyiXie XinfengTian ShuaishuaiWang FeifanWang QishanNi ShihengPan YuchunXiao Qian