AIM:To determine if the cytotail of the principal sheddase tumor necrosis factor-α converting enzyme (TACE;ADAM17) controls protein ectodomain shedding.METHODS:Site-directed mutagenesis was performed to derive TACE v...AIM:To determine if the cytotail of the principal sheddase tumor necrosis factor-α converting enzyme (TACE;ADAM17) controls protein ectodomain shedding.METHODS:Site-directed mutagenesis was performed to derive TACE variants. The resulting TACE expression plasmids with amino acid substitutions in the extracel-lular,cysteine-rich disintegrin domain (CRD) and/or deleted cytotail,along with an expression vector for the enhanced green fluorescence protein were transfected into shedding-defective M1 mutants stably expressing transmembrane L-selectin or transforming growth factor (TGF)-α. The expression levels of the TACE substrates at the cell surface were determined by flow cytometry. RESULTS:Consistent with published data,a single point mutation (C600Y) in the CRD led to shedding defi-ciency. However,removal of the cytotail from the C600Y TACE variant partially restored ectodomain cleavage of TGF-α and L-selectin. Cytotail-deleted mutants with any other substituting amino acid residues in place of Cys600 displayed similar function compared with tail-less C600Y TACE.CONCLUSION:The cytotail plays an inhibitory role,which becomes evident when it is removed from an enzyme with another mutation that affects the enzyme function.展开更多
BACKGROUND Colorectal cancer(CRC)is one of the most frequently encountered malignant tumors in clinical settings.Proteins encoded by the testis-expressed gene 14(TEX14)are imperative for spermatogenesis,necessitating ...BACKGROUND Colorectal cancer(CRC)is one of the most frequently encountered malignant tumors in clinical settings.Proteins encoded by the testis-expressed gene 14(TEX14)are imperative for spermatogenesis,necessitating intercellular bridges between germ cells.Anomalous expression of TEX14 has also been associated with the proliferation and differentiation of certain tumor cells.Recombinant A disintegrin and metalloprotease 17(ADAM17)is known as a membrane-bound protease that regulates cellular activities and signal transduction by hydrolyzing various substrate proteins on the cell membrane.We hypothesize that TEX14 and ADAM17 may serve as potential biomarkers influencing the staging,invasion,and metastasis of CRC.AIM To probe the correlation between TEX17 and ADAM17 profiles in the CRC tissues of elderly patients and their association with CRC staging,invasion,and metastasis.METHODS We gathered data from 86 elderly patients diagnosed pathologically with CRC between April 2020 and December 2023.For each patient,one sample of cancer tissue and one sample of adjacent normal tissue were harvested.Real-time fluorescence quantitative PCR measured the mRNA profiles of TEX14 and ADAM17.Immunohistochemistry ascertained the positivity rates of TEX14 and ADAM17 expressions.Clinical pathological features of neoplasm staging,invasion,and metastasis were collected,and the association between TEX14 and ADAM17 expressions and clinical pathology was evaluated.RESULTS The mRNA and expression profiles of TEX14 and ADAM17 were significantly elevated in CRC tissues.The positivity rates of TEX14 and ADAM17 proteins in CRC tissues were 70.93%and 77.91%,respectively.There were no significant differences in age,sex,pathological type,and tumor diameter between TEX14 and ADAM17-positive and-negative patients.Patients with higher tumor differentiation degree,deeper infiltration and TNM stages ranging from III to IV exhibited higher positivity rates of TEX14 and ADAM17.Patients with lymph node metastasis and distant metastasis showed higher positivity rates of TEX14 and ADAM17 than those without.Positive expressions of TEX14 and ADAM17 were highly correlated with tumor staging,invasion,and metastasis.CONCLUSION TEX14 and ADAM17 profiles were significantly elevated in the CRC tissues of elderly patients,and their high expressions were associated with tumor staging,invasion,and metastasis.展开更多
解整合素金素蛋白酶ADAM17(a disintegrin and metalloproteinase, ADAM17)可以处理80多种不同的底物,而许多底物参与恶性肿瘤的发生发展过程,目前已在多种实体瘤中检测到ADAM17的异常表达,如结肠癌、食管鳞状细胞癌、非小细胞肺癌、胃...解整合素金素蛋白酶ADAM17(a disintegrin and metalloproteinase, ADAM17)可以处理80多种不同的底物,而许多底物参与恶性肿瘤的发生发展过程,目前已在多种实体瘤中检测到ADAM17的异常表达,如结肠癌、食管鳞状细胞癌、非小细胞肺癌、胃癌、乳腺癌。对ADAM17的结构、功能与恶性肿瘤的研究进展进行综述,可为治疗恶性肿瘤的靶向药物研究提供参考。展开更多
It has been many years since "the tumor necrosis factor-a-converting enzyme”,also known as ADAM17/TACE, was described as "the enzyme that does it all” because of its role in neurodegenerative diseases and ...It has been many years since "the tumor necrosis factor-a-converting enzyme”,also known as ADAM17/TACE, was described as "the enzyme that does it all” because of its role in neurodegenerative diseases and in several physiological processes including proteolysis, adhesion, intracellular signaling, migration and proliferation. ADAM17/TACE is an integral membrane protein that belongs to the disintegrin and metalloprotease (ADAM) family. Several years ago, Romero-Grimaldi et al.展开更多
基金Supported by Grants from the National Institutes of Health,No.AG029859 the National Center of the American Heart Association,No.0330335Nthe New Jersey Commission on Cancer Research(NJCCR703010)to Fan H
文摘AIM:To determine if the cytotail of the principal sheddase tumor necrosis factor-α converting enzyme (TACE;ADAM17) controls protein ectodomain shedding.METHODS:Site-directed mutagenesis was performed to derive TACE variants. The resulting TACE expression plasmids with amino acid substitutions in the extracel-lular,cysteine-rich disintegrin domain (CRD) and/or deleted cytotail,along with an expression vector for the enhanced green fluorescence protein were transfected into shedding-defective M1 mutants stably expressing transmembrane L-selectin or transforming growth factor (TGF)-α. The expression levels of the TACE substrates at the cell surface were determined by flow cytometry. RESULTS:Consistent with published data,a single point mutation (C600Y) in the CRD led to shedding defi-ciency. However,removal of the cytotail from the C600Y TACE variant partially restored ectodomain cleavage of TGF-α and L-selectin. Cytotail-deleted mutants with any other substituting amino acid residues in place of Cys600 displayed similar function compared with tail-less C600Y TACE.CONCLUSION:The cytotail plays an inhibitory role,which becomes evident when it is removed from an enzyme with another mutation that affects the enzyme function.
基金the Ethics Committee of The Affiliated People's Hospital of Ningbo University(Approval No.2020-NB-021032).
文摘BACKGROUND Colorectal cancer(CRC)is one of the most frequently encountered malignant tumors in clinical settings.Proteins encoded by the testis-expressed gene 14(TEX14)are imperative for spermatogenesis,necessitating intercellular bridges between germ cells.Anomalous expression of TEX14 has also been associated with the proliferation and differentiation of certain tumor cells.Recombinant A disintegrin and metalloprotease 17(ADAM17)is known as a membrane-bound protease that regulates cellular activities and signal transduction by hydrolyzing various substrate proteins on the cell membrane.We hypothesize that TEX14 and ADAM17 may serve as potential biomarkers influencing the staging,invasion,and metastasis of CRC.AIM To probe the correlation between TEX17 and ADAM17 profiles in the CRC tissues of elderly patients and their association with CRC staging,invasion,and metastasis.METHODS We gathered data from 86 elderly patients diagnosed pathologically with CRC between April 2020 and December 2023.For each patient,one sample of cancer tissue and one sample of adjacent normal tissue were harvested.Real-time fluorescence quantitative PCR measured the mRNA profiles of TEX14 and ADAM17.Immunohistochemistry ascertained the positivity rates of TEX14 and ADAM17 expressions.Clinical pathological features of neoplasm staging,invasion,and metastasis were collected,and the association between TEX14 and ADAM17 expressions and clinical pathology was evaluated.RESULTS The mRNA and expression profiles of TEX14 and ADAM17 were significantly elevated in CRC tissues.The positivity rates of TEX14 and ADAM17 proteins in CRC tissues were 70.93%and 77.91%,respectively.There were no significant differences in age,sex,pathological type,and tumor diameter between TEX14 and ADAM17-positive and-negative patients.Patients with higher tumor differentiation degree,deeper infiltration and TNM stages ranging from III to IV exhibited higher positivity rates of TEX14 and ADAM17.Patients with lymph node metastasis and distant metastasis showed higher positivity rates of TEX14 and ADAM17 than those without.Positive expressions of TEX14 and ADAM17 were highly correlated with tumor staging,invasion,and metastasis.CONCLUSION TEX14 and ADAM17 profiles were significantly elevated in the CRC tissues of elderly patients,and their high expressions were associated with tumor staging,invasion,and metastasis.
文摘解整合素金素蛋白酶ADAM17(a disintegrin and metalloproteinase, ADAM17)可以处理80多种不同的底物,而许多底物参与恶性肿瘤的发生发展过程,目前已在多种实体瘤中检测到ADAM17的异常表达,如结肠癌、食管鳞状细胞癌、非小细胞肺癌、胃癌、乳腺癌。对ADAM17的结构、功能与恶性肿瘤的研究进展进行综述,可为治疗恶性肿瘤的靶向药物研究提供参考。
基金supported by the Spanish Consejería de Innovación,Ciencia y Empleo,Junta de Andalucía(P10CTS6639)Ministerio de Econmía y Competitividad(BFU 2015-6852-R,MINECO/FEDER)(both to CC)
文摘It has been many years since "the tumor necrosis factor-a-converting enzyme”,also known as ADAM17/TACE, was described as "the enzyme that does it all” because of its role in neurodegenerative diseases and in several physiological processes including proteolysis, adhesion, intracellular signaling, migration and proliferation. ADAM17/TACE is an integral membrane protein that belongs to the disintegrin and metalloprotease (ADAM) family. Several years ago, Romero-Grimaldi et al.
