Ask about this productRelated genes to: TSKS Blocking Peptide
- Gene:
- TSKS NIH gene
- Name:
- testis specific serine kinase substrate
- Previous symbol:
- -
- Synonyms:
- TSSKS, PPP1R161
- Chromosome:
- 19q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 2009-02-23
- Date modifiied:
- 2016-01-26
Related products to: TSKS Blocking Peptide
Related articles to: TSKS Blocking Peptide
- Spermiogenesis is a unique process, in which round spermatids undergo morphological changes to form spermatozoa. Serine/Threonine Kinase 33 (STK33), a member of the serine/threonine protein kinase family, plays a pivotal role in spermiogenesis, manifested by the infertile phenotype of Stk33 knockout mice and patients carrying STK33 mutations. To date, the mechanism by which STK33 promotes spermiogenesis is not fully understood. Here we aimed to identify germ cell-specific proteins that interact with STK33. Using immunoprecipitation and mass spectrometry, 13 proteins were identified that potentially interact with STK33 in testicular germ cells. By comparing the expression patterns of the candidate genes in testicular germ cells, we selected Y-Box Binding Protein 2 (YBX2) and Testis Specific Serine Kinase Substrate (TSKS) for validation. When co-expressed in cultured cells, TSKS was immunoprecipitated by STK33, and vice versa. Furthermore, STK33 was recruited to the TSKS foci, likely through interaction with TSKS. Although proximity ligation assay demonstrated that STK33 and YBX2 form the complex in germ cells, their interaction was not recapitulated in cultured cells. Phosphorylation assays showed that STK33 was unable to phosphorylate both YBX2 and TSKS in vitro. Overall, these results suggest that STK33 regulates spermiogenesis through TSKS and YBX2, which warrants further investigation in vivo. - Source: PubMed
Publication date: 2025/02/05
Cai YingMa JingWang ShusongLi Huaibiao - Cutaneous squamous cell carcinomas (cSCCs) are the second most common human cancer and have been characterized by RNA sequencing (RNA-Seq); however, the transferability of findings from individual studies may be limited by small sample sizes and diverse analysis protocols. - Source: PubMed
Bencomo TomasLee Carolyn S - Spermatozoa have a streamlined shape to swim through the oviduct to fertilize oocytes. To become svelte spermatozoa, spermatid cytoplasm must be eliminated in several steps including sperm release, which is part of spermiation. Although this process has been well observed, the molecular mechanisms that underlie it remain unclear. In male germ cells, there are membraneless organelles called nuage, which are observed by electron microscopy in various forms of dense material. Reticulated body (RB) and chromatoid body remnant (CR) are two types of nuage in spermatids, but the functions of both are unknown. Using CRISPR/Cas9 technology, we deleted the entire coding sequence of testis-specific serine kinase substrate (TSKS) in mice and demonstrate that TSKS is essential for male fertility through the formation of both RB and CR, prominent sites of TSKS localization. Due to the lack of TSKS-derived nuage (TDN), the cytoplasmic contents cannot be eliminated from spermatid cytoplasm in knockout mice, resulting in excess residual cytoplasm with an abundance of cytoplasmic materials and inducing an apoptotic response. In addition, ectopic expression of TSKS in cells results in formation of amorphous nuage-like structures; dephosphorylation of TSKS helps to induce nuage, while phosphorylation of TSKS blocks the formation. Our results indicate that TSKS and TDN are essential for spermiation and male fertility by eliminating cytoplasmic contents from the spermatid cytoplasm. - Source: PubMed
Publication date: 2023/03/07
Shimada KeisukePark SoojinOura SeiyaNoda TaichiMorohoshi AkaneMatzuk Martin MIkawa Masahito - The recurrence of cutaneous squamous cell carcinoma (cSCC) after surgery is associated with the reprogramming of the tumor microenvironment (TME), and remains a key factor affecting its outcomes. We employed single-cell RNA sequencing (scRNA-seq) to examine the dynamic changes in epithelial cells, T cells, myeloid cells, and fibroblasts between primary and recurrent cSCC. Cell clustering, cell trajectory, cell-cell communication, and gene set enrichment analysis were used to investigate the TME heterogeneity between primary and recurrent cSCC. Gene expression differences were monitored by IHC staining. We examined the immunosuppressed microenvironment in recurrent cSCC, which exhibited a T cell-excluded and SPP1 tumor-associated macrophages (TAMs)-enriched status. In recurrent cSCC, CD8 T cells showed high exhaustion and low inflammatory features, while SPP1 TAMs displayed global pro-tumor characteristics, including decreased phagocytosis and inflammation and increased angiogenesis. Furthermore, the subgroups of SPP1 TAMs harbored distinct functions. SPP1 CD209 TAMs showed features of phagocytosis, while SPP1 CD209 TAMs tended to have a high angiogenic ability. A subpopulation of tumor-specific keratinocytes (TSKs) showed significant epithelial-mesenchymal transition (EMT) features in recurrent cSCC, probably due to their active communication with IL7R cancer-associated fibroblasts (CAFs). Moreover, we found that the pleiotropic growth factor/cytokine Midkine (MDK) could provoke different cell-cell interactions in cSCC with distinctive staging. In primary cSCC, MDK was highly expressed in fibroblasts and could promote their proliferation and block the migration of tumor cells, while in recurrent cSCC, the high expression of MDK in TSKs promoted their proliferation and metastasis. Our study provides insights into the critical mechanisms of cSCC progression, which might facilitate the development of a powerful approach for the prevention and treatment of cSCC recurrence. - Source: PubMed
Publication date: 2022/10/31
Li XinZhao ShuangBian XiaohuiZhang LiningLu LixiaPei ShiyaoDong LiangShi WenshengHuang LingjuanZhang XiyuanChen MingliangChen XiangYin Mingzhu - Human spermatogenesis requires an orchestrated expression of numerous genes in various germ cell subtypes. Therefore, the genetic landscape of male infertility is highly complex. Known genetic factors alone account for at least 15% of male infertility. However, ~40% of infertile men remain undiagnosed and are classified as idiopathic infertile men. We performed exome sequencing in 47 idiopathic infertile men (discovery cohort), followed by replication study (40 variants in 33 genes) in 844 infertile men and 709 controls using Sequenom MassARRAY® based genotyping. We report 17 variants in twelve genes that comprise both previously reported (DNAH8, DNAH17, FISP2 and SPEF2) and novel candidate genes (BRDT, CETN1, CATSPERD, GMCL1, SPATA6, TSSK4, TSKS and ZNF318) for male infertility. The latter have a strong biological nexus to human spermatogenesis and their respective mouse knockouts are concordant with human phenotypes. One candidate gene CETN1, identified in this study, was sequenced in another independent cohort of 840 infertile and 689 fertile men. Further, CETN1 variants were functionally characterized using biophysical and cell biology approaches. We demonstrate that CETN1 variant- p.Met72Thr leads to multipolar cells, fragmented nuclei during mitosis leading to cell death and show significantly perturbed ciliary disassembly dynamics. Whereas CETN1-5' UTR variant; rs367716858 leads to loss of a methylation site and increased reporter gene expression in vitro. We report a total of eight novel candidate genes identified by exome sequencing, which may have diagnostic relevance and can contribute to improved diagnostic workup and clinical management of male infertility. - Source: PubMed
Sudhakar Digumarthi V SPhanindranath RegurJaishankar ShvetaRamani AnandKalamkar Kaustubh PKumar UmeshPawar Asmita DDada RimaSingh RajenderGupta Nalini JDeenadayal MamataTolani Aarti DeenadayalSharma YogendraAnand AnuranjanGopalakrishnan JayThangaraj Kumarasamy