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
- 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 - Nonobstructive azoospermia (NOA) is the most serious form of spermatogenesis abnormalities in male infertility. Genetic factors are important to consider as elements leading to NOA. Although many pathogenic genes have been reported, the causative genes of NOA for many patients are still unknown. In this study, we found ten point mutations in the gene encoding homeodomain-interacting protein kinase 4 (HIPK4) in patients with NOA, and using in vitro studies, we determined a premature termination point mutation (p. Lys490∗, c.1468A>T) that can cause decreased expression of HIPK4. Our phosphoproteomic analysis of Hipk4 testes revealed phosphorylation of multiple proteins regulated by HIPK4 during spermiogenesis. We also confirmed that a substrate of HIPK4 with four downregulated phosphorylation sites matching the xSPx motif is the known manchette-related protein RIMS-binding protein 3, which is required for sperm head morphogenesis. Therefore, we conclude HIPK4 regulates the phosphorylation of manchette protein RIMS-binding protein 3 and plays essential roles in sperm head shaping and male fertility. - Source: PubMed
Publication date: 2022/08/02
Liu XiaofeiZang ChunyanWu YifeiMeng RuChen YuJiang TaoWang ChengYang XiaoyuGuo YueshuaiSitu ChenghaoHu ZhibinZhang JunGuo Xuejiang - Homeodomain-interacting protein kinases (HIPKs) are a family of four conserved proteins essential for vertebrate development, as demonstrated by defects in the eye, brain, and skeleton that culminate in embryonic lethality when multiple HIPKs are lost in mice. While HIPKs are essential for development, functional redundancy between the four vertebrate HIPK paralogues has made it difficult to compare their respective functions. Because understanding the unique and shared functions of these essential proteins could directly benefit the fields of biology and medicine, we addressed the gap in knowledge of the four vertebrate HIPK paralogues by studying them in the fruit fly Drosophila melanogaster, where reduced genetic redundancy simplifies our functional assessment. The single hipk present in the fly allowed us to perform rescue experiments with human HIPK genes that provide new insight into their individual functions not easily assessed in vertebrate models. Furthermore, the abundance of genetic tools and established methods for monitoring specific developmental pathways and gross morphological changes in the fly allowed for functional comparisons in endogenous contexts. We first performed rescue experiments to demonstrate the extent to which each of the human HIPKs can functionally replace Drosophila Hipk for survival and morphological development. We then showed the ability of each human HIPK to modulate Armadillo/β-catenin levels, JAK/STAT activity, proliferation, growth, and death, each of which have previously been described for Hipks, but never all together in comparable tissue contexts. Finally, we characterized novel developmental phenotypes induced by human HIPKs to gain insight to their unique functions. Together, these experiments provide the first direct comparison of all four vertebrate HIPKs to determine their roles in a developmental context. - Source: PubMed
Kinsey Stephen DVinluan Justin PShipman Gerald AVerheyen Esther M - Mammalian spermiogenesis is a remarkable cellular transformation, during which round spermatids elongate into chromatin-condensed spermatozoa. The signaling pathways that coordinate this process are not well understood, and we demonstrate here that homeodomain-interacting protein kinase 4 (HIPK4) is essential for spermiogenesis and male fertility in mice. HIPK4 is predominantly expressed in round and early elongating spermatids, and knockout males are sterile, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. mutant sperm have reduced oocyte binding and are incompetent for in vitro fertilization, but they can still produce viable offspring via intracytoplasmic sperm injection. Optical and electron microscopy of HIPK4-null male germ cells reveals defects in the filamentous actin (F-actin)-scaffolded acroplaxome during spermatid elongation and abnormal head morphologies in mature spermatozoa. We further observe that HIPK4 overexpression induces branched F-actin structures in cultured fibroblasts and that HIPK4 deficiency alters the subcellular distribution of an F-actin capping protein in the testis, supporting a role for this kinase in cytoskeleton remodeling. Our findings establish HIPK4 as an essential regulator of sperm head shaping and potential target for male contraception. - Source: PubMed
Publication date: 2020/03/12
Crapster J AaronRack Paul GHellmann Zane JLe Austen DAdams Christopher MLeib Ryan DElias Joshua EPerrino JohnBehr BarryLi YanfengLin JenniferZeng HongChen James K