Spink13, an Epididymis-specific Gene of the Kazal-type Serine Protease Inhibitor (SPINK) Family, Is Essential for the Acrosomal Integrity and Male Fertility

Ma, Li; Yu, Huan; Ni, Zimei; Hu, Shuanggang; Wei, Ma; Chu, Chengcai; Liu, Qiang; Zhang, Yonglian

doi:10.1074/jbc.m112.445866

Cited by 40 publications

(42 citation statements)

References 63 publications

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“…All of the protease inhibitors showed regionspecifi c localizations and their expression was controlled by testis-specifi c factors suggesting a role for the inhibitors in the regulation of sperm maturation. Recently, SPINK13 was also identifi ed in the epididymis [ 81 ]. SPINK13 was secreted into the epididymal lumen where it associated with the acrosomal region of maturing spermatozoa.…”

Section: Protein Processingmentioning

confidence: 99%

Role of Posttranslational Protein Modifications in Epididymal Sperm Maturation and Extracellular Quality Control

Cornwall

2014

Advances in Experimental Medicine and Biology

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The epididymal lumen is a complex microenvironment in which spermatozoa acquire motility and fertility. Spermatozoa are synthetically inactive and therefore the maturation process requires their interaction with proteins that are synthesized and secreted in a highly regionalized manner by the epididymal epithelium. In addition to the integration of epididymal secretory proteins, posttranslational modifications of existing sperm proteins are important for sperm maturation and acquisition of fertilizing potential. Phosphorylation, glycosylation, and processing are several of the posttranslational modifications that sperm proteins undergo during epididymal transit resulting in changes in protein function and localization ultimately leading to mature spermatozoa. In addition to these well-characterized modifications, protein aggregation and cross-linking also occur within the epididymal lumen and may represent unique mechanisms for controlling protein function including that for maturation as well as for extracellular quality control.

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Section: Protein Processingmentioning

confidence: 99%

Role of Posttranslational Protein Modifications in Epididymal Sperm Maturation and Extracellular Quality Control

Cornwall

2014

Advances in Experimental Medicine and Biology

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“…The SPINK family has more than 10 members in humans, including SPINK1, SPINK2, SPINK4-9, SPINK13, and SPINK14 [7, 8]. Recent studies have found that mutant male mice with reduced SPINK2 levels exhibit impaired fertility [19].…”

Section: Discussionmentioning

confidence: 99%

“…SPINK13 is an epididymis-specific gene that functions as a protease inhibitor necessary for the regulation of critical proteases involved in early signalling events during fertilization [21]. SPINK13 also has a regulatory effect on the acrosomal reaction, and it maintains an equilibrium of protease activity for essential processes that preserve sperm and tissue integrity without affecting capacitation [8]. The SPINK13 protein has the characteristic signature of serine proteases inhibitors containing an N-terminal signal peptide accompanied with a Kazal domain [8], but the function of its serine protease-inhibitory activity is still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The SPINK13 protein has the characteristic signature of serine protease inhibitors consisting of an N-terminal signal peptide accompanied with a Kazal domain, and it belongs to the SPINK family, which has more than 10 SPINK members in humans [7, 8]. All SPINK members have been reported to be responsible for regulating serine protease activity or preventing uncontrolled proteolysis [9].…”

Section: Introductionmentioning

confidence: 99%

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Downregulation of SPINK13 Promotes Metastasis by Regulating uPA in Ovarian Cancer Cells

Cai

Zhang

Dong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ovarian cancer (OC) is the fifth leading cause of cancer-related death in women, and it is difficult to diagnose at an early stage. The purpose of this study was to explore the prognostic biological markers of OC. Methods: Univariate Cox regression analysis was used to identify genes related to OC prognosis from the Cancer Genome Atlas(TCGA) database. Immunohistochemistry was used to analyse the level of SPINK13 in OC and normal tissues. Cell proliferation, apoptosis and invasion were performed using MTT assay, flow cytometric analysis and Transwell assay, respectively. Results: We identified the Kazal-type serine protease inhibitor-13 (SPINK13) gene related to OC prognosis from the Cancer Genome Atlas (TCGA) database by univariate Cox regression analysis. Overexpression of SPINK13 was associated with higher overall survival rate in OC patients. Immunohistochemistry showed that the level of SPINK13 protein was significantly lower in OC tissues than in normal tissues (P < 0.05).In vitro experiments showed that the overexpression of SPINK13 inhibited cellular proliferation and promoted apoptosis. Moreover, SPINK13 inhibited cell migration and epithelial to mesenchymal transition (EMT). SPINK13 was found to inhibit the expression of urokinase-type plasminogen activator (uPA), while recombinant uPA protein could reverse the inhibitory effect of SPINK13 on OC metastasis. Conclusion: These results indicate that SPINK13 functions as a tumour suppressor. The role of SPINK13 in cellular proliferation, apoptosis and migration is uPA dependent, and SPINK13 may be used as a potential biomarker for diagnosis and targeted therapy in OC.

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“…The use of molecular biomarkers has been studied to assist the early diagnosis of prostate pathologies in dogs, but these methods are not yet routinely available (MUSSEL et al, 2010). Furthermore, studies of canine reproduction contribute to the physiological knowledge of other species, which can enable the development of new biotechnologies and facilitate the treatment of diseases related to sperm maturation (MA et al, 2013).…”

Section: Proteins Of the Canine Sp As Biomarkers Of Reproductive Tracmentioning

confidence: 99%

Proteins of the canine seminal plasma

et al. 2016

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Spink13, an Epididymis-specific Gene of the Kazal-type Serine Protease Inhibitor (SPINK) Family, Is Essential for the Acrosomal Integrity and Male Fertility

Cited by 40 publications

References 63 publications

Role of Posttranslational Protein Modifications in Epididymal Sperm Maturation and Extracellular Quality Control

Role of Posttranslational Protein Modifications in Epididymal Sperm Maturation and Extracellular Quality Control

Downregulation of SPINK13 Promotes Metastasis by Regulating uPA in Ovarian Cancer Cells

Proteins of the canine seminal plasma

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