scholarly journals Human High Temperature Requirement Serine Protease A1 (HTRA1) Degrades Tau Protein Aggregates

2012 ◽  
Vol 287 (25) ◽  
pp. 20931-20941 ◽  
Author(s):  
Annette Tennstaedt ◽  
Simon Pöpsel ◽  
Linda Truebestein ◽  
Patrick Hauske ◽  
Anke Brockmann ◽  
...  
Keyword(s):  
High Temperature ◽  
Serine Protease ◽  
Tau Protein ◽  
Protein Aggregates ◽  
Temperature Requirement

High-temperature requirement factor A3 (Htra3): A novel serine protease and its potential role in ovarian function and ovarian cancers

2010 ◽  
Vol 327 (1-2) ◽  
pp. 13-18 ◽  
Author(s):  
Marissa A. Bowden ◽  
Ann E. Drummond ◽  
Peter J. Fuller ◽  
Lois A. Salamonsen ◽  
Jock K. Findlay ◽  
...  
Keyword(s):  
High Temperature ◽  
Serine Protease ◽  
Potential Role ◽  
Ovarian Function ◽  
Ovarian Cancers ◽  
Temperature Requirement

The trimeric serine protease HtrA1 forms a cage-like inhibition complex with an anti-HtrA1 antibody

2015 ◽  
Vol 472 (2) ◽  
pp. 169-181 ◽  
Author(s):  
Claudio Ciferri ◽  
Michael T. Lipari ◽  
Wei-Ching Liang ◽  
Alberto Estevez ◽  
Julie Hang ◽  
...  
Keyword(s):  
High Temperature ◽  
Macular Degeneration ◽  
Serine Protease ◽  
Antibody Binding ◽  
Age Related Macular Degeneration ◽  
Inhibitory Mechanism ◽  
Blocking Antibody ◽  
Temperature Requirement ◽  
Age Related

The high temperature requirement A1 (HtrA1) protease is implicated in many pathological processes, including the age-related macular degeneration (AMD). We identified a blocking antibody binding to the HTRA1 complex trimer and were able to elucidate an unusual inhibitory mechanism by structural and biochemical experiments.

284.Expression of HtrA1, 2 and 3 in human endometrial cancer

2004 ◽  
Vol 16 (9) ◽  
pp. 284
Author(s):  
M. A. Bowden ◽  
L. A. Di Nezza ◽  
T. Jobling ◽  
L. A. Salamonsen ◽  
G. Nie
Keyword(s):  
Endometrial Cancer ◽  
High Temperature ◽  
Serine Protease ◽  
Cancer Progression ◽  
Serine Proteases ◽  
Genomic Structure ◽  
Normal Endometrium ◽  
Tissue Samples ◽  
Subtraction Hybridization ◽  
Temperature Requirement

The mammalian HtrA family consists of serine proteases with distinct domains homologous to the bacterial high temperature requirement factor (HtrA). Three human HtrA members have been reported: HtrA1 (PRSS11 or L56), HtrA2 (OMI) and HtrA3 (PRSP). The function of HtrA1 is not well characterised, but it has been shown to be downregulated in malignant tissues (1–3) indicating that the downregulation of HtrA1 is associated with cancer progression. HtrA2 regulates apoptosis by interacting with X-linked inhibitors of apoptosis (XIAP) thus preventing the caspase-inhibitory function of XIAP (4). The function of newly identified HtrA3 is not known, however it shares a high degree of sequence and domain homologies with HtrA1 and may therefore share a functional similarity with HtrA1 (5). Endometrial cancer (EC) is a prevalent gynaecological cancer, commonly affecting women after menopause. In this study we examined the expression of HtrA1, 2 and 3 in EC. Reverse transcriptase-PCR (semi-quantitative) analysis showed decreased mRNA expression of both HtrA1 and HtrA3, but no significant change for HtrA2, in EC tissue samples compared to normal endometrium. We then determined the protein level of expression and the cellular localisation of all three HtrA members in EC progression using immunohistochemistry. HtrA1 and HtrA3 showed a similar pattern of expression and both decreased dramatically with the progression of cancer from grade 1 through to 3. Surprisingly, HtrA2 protein expression was also decreased with cancer progression, but the decline was not as dramatic as that for HtrA1 and HtrA3. Interestingly, considerably less staining was observed for all three HtrA proteins in grade 3 cancer tissues. These data suggest that decreased expression of HtrA proteins, particularly HtrA1 and HtrA3, is associated with the progression of endometrial cancer. (1) Nie, G., Hampton, A., Li, Y., Findlay, J., Salamonsen, L.A. (2003) Identification and cloning of two isoforms of human high-temperature requirement factor A3 (HtrA3), characterization of its genomic structure and comparison of its tissue distribution with HtrA1 and HtrA2. Biochem. J. 371, 39–48. (2) van Loo, G., van Gurp, M., Depuydt, B., Srinivasula, S.M., Rodriguez, I., Alnemri, E.S., Gevaert, K., Vandekerckhove, J., Declercq, W., Vandenabeele, P. (2002) The serine protease OMI/HtrA2 is released from mitochondria during apoptosis. OMI interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Diff. 9, 20–26. (3) Chien, J., Staub, J., Hu, S., Erickson-Johnson, M.R., Couch, F.J., Smith, D.I., Crowl, R.M., Kaufmann, S., Shridhar, V. (2004) A candidate tumour supressor HtrA1 is down-regulated in ovarian cancer. Oncogene 23, 1636–1644. (4) Shridhar, V., Sen, A., Chien, J., Staub, J., Avula, R., Kovats, S., Lee, J., Lillie, J., Smith, D.I. (2002) Identification of underexpressed genes in early- and late-stage primary ovarian tumours by suppression subtraction hybridization. Cancer Res. 62, 262–270. (5) Baldi, A., De Luca, A., Morini, M., Battista, T., Felsani, A., Baldi, F., Catricala, C., Amantea, A., Noonan, D. M., Albini, A., Ciorgio, P., Lombardi, D., Paggi, M. G. (2002) The HtrA1 serine protease is down-regulated during human melanoma progression and represses growth of metastatic melanoma cells. Oncogene 21, 6684–6688.

scholarly journals Expression and Localization of the Serine Proteases High-Temperature Requirement Factor A1, Serine Protease 23, and Serine Protease 35 in the Mouse Ovary

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 5070-5077 ◽  
Author(s):  
Patrik Wahlberg ◽  
Åsa Nylander ◽  
Nina Ahlskog ◽  
Kui Liu ◽  
Tor Ny
Keyword(s):  
High Temperature ◽  
Serine Protease ◽  
Granulosa Cells ◽  
Serine Proteases ◽  
Expression Patterns ◽  
Follicular Development ◽  
Ovarian Stroma ◽  
Temperature Requirement ◽  
Extracellular Matrix Components ◽  
Preovulatory Follicles

Proteolytic degradation of extracellular matrix components has been suggested to play an essential role in the occurrence of ovulation. Recent studies in our laboratory have indicated that the plasminogen activator and matrix metalloproteinase systems, which were previously believed to be crucial for ovulation, are not required in this process. In this study we have used a microarray approach to identify new proteases that are involved in ovulation. We found three serine proteases that were relatively highly expressed during ovulation: high-temperature requirement factor A1 (HtrA1), which was not regulated much during ovulation; serine protease 23 (PRSS23), which was down-regulated by gonadotropins; and serine protease 35 (PRSS35), which was up-regulated by gonadotropins. We have further investigated the expression patterns of these proteases during gonadotropin-induced ovulation in immature mice and in the corpus luteum (CL) of pseudopregnant mice. We found that HtrA1 was highly expressed in granulosa cells throughout follicular development and ovulation, as well as in the forming and regressing CL. PRSS23 was highly expressed in atretic follicles, and it was expressed in the ovarian stroma and theca tissues just before ovulation. PRSS35 was expressed in the theca layers of developing follicles. It was also highly induced in granulosa cells of preovulatory follicles. PRSS35 was also expressed in the forming and regressing CL. These data suggest that HtrA1 and PRSS35 may be involved in ovulation and CL formation and regression, and that PRSS23 may play a role in follicular atresia.

scholarly journals Detrimental Role for Human High Temperature Requirement Serine Protease A1 (HTRA1) in the Pathogenesis of Intervertebral Disc (IVD) Degeneration

2012 ◽  
Vol 287 (25) ◽  
pp. 21335-21345 ◽  
Author(s):  
André N. Tiaden ◽  
Marina Klawitter ◽  
Vanda Lux ◽  
Ali Mirsaidi ◽  
Gregor Bahrenberg ◽  
...  
Keyword(s):  
High Temperature ◽  
Intervertebral Disc ◽  
Serine Protease ◽  
Temperature Requirement ◽  
Ivd Degeneration

scholarly journals The crystal structure of Mycobacterium tuberculosis high-temperature requirement A protein reveals an autoregulatory mechanism

2018 ◽  
Vol 74 (12) ◽  
pp. 803-809
Author(s):  
Arvind Kumar Gupta ◽  
Debashree Behera ◽  
Balasubramanian Gopal
Keyword(s):  
Crystal Structure ◽  
Mycobacterium Tuberculosis ◽  
High Temperature ◽  
Catalytic Domain ◽  
Pdz Domain ◽  
Regulatory Pathways ◽  
Inactive Conformation ◽  
Temperature Requirement ◽  
Autoregulatory Mechanism

The crystal structure of Mycobacterium tuberculosis high-temperature requirement A (HtrA) protein was determined at 1.83 Å resolution. This membrane-associated protease is essential for the survival of M. tuberculosis. The crystal structure reveals that interactions between the PDZ domain and the catalytic domain in HtrA lead to an inactive conformation. This finding is consistent with its proposed role as a regulatory protease that is conditionally activated upon appropriate environmental triggers. The structure provides a basis for directed studies to evaluate the role of this essential protein and the regulatory pathways that are influenced by this protease.

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