scholarly journals Inherited diseases caused by mutations in cathepsin protease genes

FEBS Journal ◽  
2017 ◽  
Vol 284 (10) ◽  
pp. 1437-1454 ◽  
Author(s):  
Stephanie Ketterer ◽  
Alejandro Gomez-Auli ◽  
Larissa E. Hillebrand ◽  
Agnese Petrera ◽  
Anett Ketscher ◽  
...  
Keyword(s):  
Inherited Diseases ◽  
Cathepsin Protease

scholarly journals Development and Carcinogenesis: Roles of GATA Factors in the Sympathoadrenal and Urogenital Systems

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 299
Author(s):  
Takashi Moriguchi
Keyword(s):  
Transcription Factors ◽  
Developmental Process ◽  
Current Knowledge ◽  
Gynecologic Cancers ◽  
Inherited Diseases ◽  
Gata Factors ◽  
Transcriptional Regulatory ◽  
Gata Family

The GATA family of transcription factors consists of six proteins (GATA1-6) that control a variety of physiological and pathological processes. In particular, GATA2 and GATA3 are coexpressed in a number of tissues, including in the urogenital and sympathoadrenal systems, in which both factors participate in the developmental process and tissue maintenance. Furthermore, accumulating studies have demonstrated that GATA2 and GATA3 are involved in distinct types of inherited diseases as well as carcinogenesis in diverse tissues. This review summarizes our current knowledge of how GATA2 and GATA3 participate in the transcriptional regulatory circuitry during the development of the sympathoadrenal and urogenital systems, and how their dysregulation results in the carcinogenesis of neuroblastoma, renal urothelial, and gynecologic cancers.

scholarly journals Special Issue “Molecular Basis of Inherited Diseases in Companion Animals”

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 68
Author(s):  
Steven G. Friedenberg ◽  
Danika L. Bannasch
Keyword(s):  
Molecular Basis ◽  
Companion Animals ◽  
Special Issue ◽  
Inherited Diseases ◽  
The Past

The study of inherited diseases in companion animals has exploded over the past 15 years since the publication of the first dog genome in 2005 [...]

scholarly journals The Molecular Physiology of Sodium- and Proton-Coupled Solute Transporters

Physiology ◽  
1998 ◽  
Vol 13 (3) ◽  
pp. 123-131 ◽  
Author(s):  
Angela Steel ◽  
Matthias A. Hediger
Keyword(s):  
Xenopus Laevis ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Xenopus Laevis Oocytes ◽  
Missense Mutations ◽  
Molecular Physiology ◽  
Inherited Diseases ◽  
Biophysical Analysis ◽  
Solute Transporters

The expression of cloned Na+- and H+-coupled solute transporters in Xenopus laevis oocytes has permitted detailed molecular and biophysical analysis and illuminated unique mechanistic features. The identification of missense mutations in inherited diseases and site-directed mutagenesis studies have enhanced our understanding of their roles in physiological and pathological processes.

Structure, function, and relevance of thyroid peroxidase in inherited diseases of the thyroid

1997 ◽  
Vol 4 (5) ◽  
pp. 328-332 ◽  
Author(s):  
Jan J.M. de Vijlder ◽  
Hennie Bikker ◽  
Carrie Ris-Stalpers ◽  
Thomas Vulsma
Keyword(s):  
Structure Function ◽  
Thyroid Peroxidase ◽  
Inherited Diseases

scholarly journals Long-read sequence confirmed a large deletion of MYH6 and MYH7 in a family with atrial septal defect

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Sonoda ◽  
S Ohno ◽  
M Horie
Keyword(s):  
Atrial Septal Defect ◽  
Septal Defect ◽  
Break Point ◽  
Large Deletion ◽  
Single Nucleotide Variants ◽  
Genomic Libraries ◽  
Flow Cells ◽  
Inherited Diseases ◽  
Long Read ◽  
Long Range Pcr

Abstract Background Genome structural variants (SVs) have larger effect on human genome functions than single nucleotide variants (SNVs). Although short-read sequencing (SRS) is current major next generation sequencing method and has given us a great benefit to elucidate the genetic background of inherited diseases, it does not detect SVs accurately. Long-read sequencing (LRS) produces tens to thousands of kilobases reads and detects the breakpoints of complex SVs. This study aimed to confirm a large deletion, which was suspected by SRS, using LRS by Oxford Nanopore technology (ONT). Methods Genomic libraries for SRS was prepared with HaloPlex. Targeted SRS was performed for 58 genes with MiSeq. Genomic libraries for LRS were prepared using the Ligation sequencing 1D kit SQK-LSK109 (ONT). Whole genome LRS was performed with GridION X5 and R9.4 flow cells (ONT). Results The patient was a five-month-old boy with atrial septal defect (ASD) and atrial tachycardia. Though SRS failed to identify any causative SNVs, the results with SureCall software (Agilent) suspected a deletion between exon 3 to exon 26 in MYH6 encoding α heavy chains of cardiac myosin. The variants in MYH6 are known to be associated with ASD. Because a deletion between MYH6 exon 26 and MYH7 exon 27 was reported as esv2748480 on the Database of Genomic Variants, we performed long-range PCR from MYH6 intron26 to MYH7 exon26 and found an abnormal 1.5K bases PCR product only in the case. Due to high homology of MYH6 and MYH7, Sanger sequencing failed to detect the break point. In LRS, 3 flow cells generated 3.8M base-called reads containing 42G bases with N50 of 13K bases. We used NGMLR, which is a long-read mapper, to align the reads to the human reference genome (hg38). SVs were called by Sniffles detecting all types of SVs. The deletion was found to range from chr14: 23390037 to 23419824 (see figure) and did not contain other SVs. There was no pathogenic SV on ACTC1, GATA4, TBX20 and TLL1 which are genes related to ASD on Genetic Testing Registry. His mother had also ASD and harbored the same deletion. Conclusions This is the first report to identify a large deletion between MYH6 and MYH7 in the family with ASD. The combination of SRS and LRS is useful to detect SVs in patients with suspected inherited diseases but carried no causative SNVs. Funding Acknowledgement Type of funding source: None

scholarly journals Intrinsically Connected: Therapeutically Targeting the Cathepsin Proteases and the Bcl-2 Family of Protein Substrates as Co-regulators of Apoptosis

2021 ◽  
Vol 22 (9) ◽  
pp. 4669
Author(s):  
Surinder M. Soond ◽  
Maria V. Kozhevnikova ◽  
Lyudmila V. Savvateeva ◽  
Paul A. Townsend ◽  
Andrey A. Zamyatnin
Keyword(s):  
Tumor Biology ◽  
Therapeutic Targeting ◽  
Apoptosis Pathway ◽  
Apoptotic Signaling ◽  
Protein Substrates ◽  
Cathepsin Proteases ◽  
Apoptotic Protein ◽  
Intrinsic Apoptosis Pathway ◽  
Cathepsin Protease ◽  
The Relationship

Taken with the growing importance of cathepsin-mediated substrate proteolysis in tumor biology and progression, the focus and emphasis placed on therapeutic design and development is coming into fruition. Underpinning this approach is the invariable progression from the direction of fully characterizing cathepsin protease members and their substrate targets, towards targeting such an interaction with tangible therapeutics. The two groups of such substrates that have gained much attention over the years are the pro- and anti- apoptotic protein intermediates from the extrinsic and intrinsic signaling arms of the apoptosis pathway. As proteins that are central to determining cellular fate, some of them present themselves as very favorable candidates for therapeutic targeting. However, considering that both anti- and pro- apoptotic signaling intermediates have been reported to be downstream substrates for certain activated cathepsin proteases, therapeutic targeting approaches based on greater selectivity do need to be given greater consideration. Herein, we review the relationships shared by the cathepsin proteases and the Bcl-2 homology domain proteins, in the context of how the topical approach of adopting ‘BH3-mimetics’ can be explored further in modulating the relationship between the anti- and pro- apoptotic signaling intermediates from the intrinsic apoptosis pathway and their upstream cathepsin protease regulators. Based on this, we highlight important future considerations for improved therapeutic design.

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