Activity-Based Probes for the High Temperature Requirement A Serine Proteases

2020 ◽  
Vol 15 (9) ◽  
pp. 2346-2354
Author(s):  
Ho Yeon Nam ◽  
Dasom Song ◽  
Jinny Eo ◽  
Na-Eun Choi ◽  
Jong-Ah Hong ◽  
...  
Keyword(s):  
High Temperature ◽  
Serine Proteases ◽  
Temperature Requirement

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 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.

scholarly journals High-Temperature Requirement A1 (Htra1) - A Novel Regulator of Canonical Wnt Signaling

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Oriane Globus ◽  
Tamar Evron ◽  
Michal Caspi ◽  
Ronen Siman-Tov ◽  
Rina Rosin-Arbesfeld
Keyword(s):  
High Temperature ◽  
Wnt Signaling ◽  
Canonical Wnt Signaling ◽  
Temperature Requirement ◽  
Canonical Wnt

The crystal structure of an essential high-temperature requirement protein HtrA1 (Rv1223) from Mycobacterium tuberculosis reveals its unique features

2018 ◽  
Vol 74 (9) ◽  
pp. 906-921 ◽  
Author(s):  
Khundrakpam Herojit Singh ◽  
Savita Yadav ◽  
Deepak Kumar ◽  
Bichitra Kumar Biswal
Keyword(s):  
Crystal Structure ◽  
Amino Acids ◽  
Mycobacterium Tuberculosis ◽  
High Temperature ◽  
Protein Quality ◽  
Pdz Domain ◽  
Survival Strategies ◽  
Dimensional Structure ◽  
Protease Domain ◽  
Temperature Requirement

High-temperature requirement A (HtrA) proteins, which are members of the heat-shock-induced serine protease family, are involved in extracytoplasmic protein quality control and bacterial survival strategies under stress conditions, and are associated with the virulence of several pathogens; they are therefore major drug targets. Mycobacterium tuberculosis possesses three putative HtrAs: HtrA1 (Rv1223), HtrA2 (Rv0983) and HtrA3 (Rv0125). Each has a cytoplasmic region, a transmembrane helix and a periplasmic region. Here, the crystal structure of the periplasmic region consisting of a protease domain (PD) and a PDZ domain from an M. tuberculosis HtrA1 mutant (mHtrA1S387A) is reported at 2.7 Å resolution. Although the mHtrA1S387A PD shows structural features similar to those of other HtrAs, its loops, particularly L3 and LA, display different conformations. Loop L3 communicates between the PDs of the trimer and the PDZ domains and undergoes a transition from an active to an inactive conformation, as reported for an equivalent HtrA (DegS). Loop LA, which is responsible for higher oligomer formation owing to its length (50 amino acids) in DegP, is very short in mHtrA1S387A (five amino acids), as in mHtrA2 (also five amino acids), and therefore lacks essential interactions for the formation of higher oligomers. Notably, a well ordered loop known as the insertion clamp in the PDZ domain interacts with the protease domain of the adjacent molecule, which possibly aids in the stabilization of a trimeric functional unit of this enzyme. The three-dimensional structure of mHtrA1S387A presented here will be useful in the design of enzyme-specific antituberculosis inhibitors.

Behaviour of a high-temperature-requirement A (HtrA) deletion mutant of Brucella abortus in goats

1996 ◽  
Vol 60 (1) ◽  
pp. 48-50 ◽  
Author(s):  
P.H Elzer ◽  
S.D Hagius ◽  
G.T Robertson ◽  
R.W Phillips ◽  
J.V Walker ◽  
...  
Keyword(s):  
High Temperature ◽  
Brucella Abortus ◽  
Deletion Mutant ◽  
Temperature Requirement

Flowering responses to vernalization and photoperiod in annual medics (Medicago spp.)

1975 ◽  
Vol 26 (5) ◽  
pp. 831 ◽  
Author(s):  
NM Clarkson ◽  
JS Russell
Keyword(s):  
High Temperature ◽  
Flowering Time ◽  
Vernalization Requirement ◽  
Vernalization Response ◽  
The Third ◽  
Long Day ◽  
Temperature Requirement ◽  
New Finding ◽  
Annual Medics

The three processes thought to control flowering times in annual medics (Medicago spp.) are a vernalization requirement, a long day requirement and a high temperature requirement. To examine the first two processes, seed of seven cultivars of six species was vernalized at 1�C for periods of up to 11 weeks, then grown to flowering under three photoperiods in a glasshouse. To study the third process, the time to flowering of selected treatments from this expcrirnent was compared with flowering data from plants grown in the field at a range of temperatures lower than in the glasshouse. Vernalization and photoperiod caused large shifts in flowering time but the effects varied widely among species. M. scutellata was almost insensitive to both factors but in M. rugosa acceleration of up to 91 days was caused by treatment. Vernalization and short dark periods were additive in accelerating flowering and largely able to substitute for each other. Species flowered almost simultaneously when given their most favourable conditions for flowering. High temperature accelerated flowering in all species studied. However, in species other than M. scutellata it was necessary for a vernalization requirement to be met before this effect was observed. A new finding was that the vernalization response in M. truncatula and M. littoralis was largely reversed after more than 7 weeks of vernalization. This suggests a previously undetected flowering mechanism in these species.

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