Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS.

Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS.

ESPL1 / separase, a cysteine ​​endopeptidase, is a key player in centrosome duplication and mitotic sister chromatid separation. aberrant expression and / or modified separase proteolytic activity associated with centrosome amplification, aneuploidy, tumorigenesis and progression of the disease. Since centrosome changes are common and early feature detected in patients with myelodysplastic syndrome (MDS) and the deviation cytogenetic play an important role in the risk stratification of disease, we tested the activity of separase at the level of single cells in the marrow samples 67 bone obtained from patients with MDS, secondary acute myeloid leukemia (SAML), de novo acute myeloid leukemia (AML) and healthy controls by flow cytometric separase activity test.

Separase Activity Distribution (SAD) value, calculated for the size of the cells with prominent separase activity in the samples analyzed, tested for correlation with the centrosome, karyotype and gene mutation status. We find the values ​​of SAD are higher in the patient’s bone marrow cells compared to the corresponding SAML MDS patients’ cells.

This concurs with the increased incidence of aberrant centrosome phenotype in MDS vs SAML samples. No correlation was found between the values ​​of SAD and mutation status karyotype / gen. During the follow-up of four MDS patients we observed an increase in the value of the SAD after transformation into SAML, two patients SAD value decreases during azacitidine therapy. cell culture experiments using cells of MDS-L as an in vitro model of MDS revealed that treatment with rigosertib, PLK1 inhibitors and therapeutic drugs known to induce G2 / M capture, results in a decrease in the value of SAD.

In conclusion, the appearance of cells with high levels of activity separase unusual, as indicated by the increased value of the SAD, agreed with the transformation of MDS to SAML and may reflect the potentially separase dysregulation contributes to clonal evolution during the progression of MDS. Separase measurement activities may therefore be useful as a new additional molecular markers for monitoring the disease.

Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS.
Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS.

Separase Detection Sensor Cleavage Live Event Using Mouse oocytes.

Separase proteolytic eliminate cohesin complex of sister chromatid arm in meiosis I, which are essential for chromosome segregation. Regulation separase activity is essential for proper cell cycle progression and proper chromosome segregation. Onset separase endogenous activity has not been observed in oocytes.

We live here describe a method for detecting separase activity in vivo mouse oocytes. This method utilizes previously described cleavage sensor consists of H2B-mCherry fused with Scc1 (aa 107-268) -YFP. Sensors division loaded on chromosome through the H2B-tag, and the signals from both mCherry and YFP visible. Upon activation separase Scc1 fragment cleaved and YFP dissociates from chromosomes. Changes in the ratio between mCherry and YFP fluorescence intensity is reading separase activity.


anaphase onset is irreversible cell cycle transitions triggered by protease activation Separase. Separase splitting Mcd1 (also known as Scc1) subunit of cohesin, a protein complex that physically connects the sister chromatids, triggering chromatid separation. Separase governed by degradation of anaphase inhibitor Securin freeing of inhibition of complex Separase Securin / Separase. In many organisms, Securin important not show that Separase governed by additional mechanisms.

Anti-Phospho-Rsk-1/2/3/4 (S221/227/S218/232) antibody

STJ90596 200 µl
EUR 236.4
Description: Rabbit polyclonal to Phospho-Rsk-1/2/3/4 (S221/227/S218/232).

S18886

C5387-10 10 mg
EUR 182.4
Description: IC50: 16.4 nM for TP receptor S18886 is a potent thromboxane A2 (TP) inhibitor. The lipid mediator thromboxane A2 (TXA2) plays a critical role in platelet aggregation and vascular and bronchial smooth muscle constriction.

S18886

C5387-5 5 mg
EUR 141.6
Description: IC50: 16.4 nM for TP receptor S18886 is a potent thromboxane A2 (TP) inhibitor. The lipid mediator thromboxane A2 (TXA2) plays a critical role in platelet aggregation and vascular and bronchial smooth muscle constriction.

S26948

B7471-10 10 mg
EUR 466.8

S26948

B7471-50 50 mg
EUR 1771.2

S63845

B1819-1000 each
EUR 489.6

S63845

B1819-250 each
EUR 189.6

S63845

A8737-1 1 mg
EUR 212.4
Description: S63845 is a small molecule MCL1 inhibitor with Ki < 1.2 nM [1].Myeloid cell leukemia 1 (MCL1) is a pro-survival protein and belongs to BCL-2 family proteins.

S63845

A8737-10 10 mg
EUR 895.2
Description: S63845 is a small molecule MCL1 inhibitor with Ki < 1.2 nM [1].Myeloid cell leukemia 1 (MCL1) is a pro-survival protein and belongs to BCL-2 family proteins.

S63845

A8737-25 25 mg
EUR 1730.4
Description: S63845 is a small molecule MCL1 inhibitor with Ki < 1.2 nM [1].Myeloid cell leukemia 1 (MCL1) is a pro-survival protein and belongs to BCL-2 family proteins.

S63845

A8737-5 5 mg
EUR 547.2
Description: S63845 is a small molecule MCL1 inhibitor with Ki < 1.2 nM [1].Myeloid cell leukemia 1 (MCL1) is a pro-survival protein and belongs to BCL-2 family proteins.

S14161

GL4789-1MG 1 mg
EUR 171.6

S14161

GL4789-5MG 5 mg
EUR 440.4

S16961

HY-U00281 5mg
EUR 1383.6

S63845

HY-100741 100mg
EUR 2043.6

S55746

HY-117288 100mg
EUR 2402.4

S26131

HY-122136 1mg
EUR 129.6

S29434

HY-122614 1mg
EUR 224.4

S49076

HY-12965 100mg
EUR 1398

S14161

GL4789-1 1
EUR 116.1

S14161

GL4789-5 5
EUR 346.1

Phospho- PAK1/2/3 (S144+ S141+ S139) Antibody

ABD2948 100 ug
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Phospho-PAK1 / 2 / 3 (S144+S141+S139) Antibody

20-abx217621
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  • 100 ug
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Monoclonal SLC38A1 / NaT2 Antibody (clone S104-32), Clone: S104-32

APR10075G 0.05mg
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Description: A Monoclonal antibody against Human SLC38A1 / NaT2 (clone S104-32). The antibodies are raised in Mouse and are from clone S104-32. This antibody is applicable in WB and IHC-P, ICC

Monoclonal ANK3 / ANKYRIN-G Antibody (clone S106-20), Clone: S106-20

APR11412G 0.05mg
EUR 580.8
Description: A Monoclonal antibody against Human ANK3 / ANKYRIN-G (clone S106-20). The antibodies are raised in Mouse and are from clone S106-20. This antibody is applicable in WB and IHC-P

Monoclonal ANK2 / Ankyrin B Antibody (aa203-496, clone S105-17), Clone: S105-17

APR11410G 0.05mg
EUR 580.8
Description: A Monoclonal antibody against Human ANK2 / Ankyrin B (aa203-496, clone S105-17). The antibodies are raised in Mouse and are from clone S105-17. This antibody is applicable in WB and IHC-P, ICC

Human S100A1/S100(Protein S100-A1) ELISA Kit

EH0380 96T
EUR 681.12
Description: Method of detection: Double Antibody, Sandwich ELISA;Reacts with: Homo sapiens;Sensitivity: 0.094 ng/ml

Polyclonal TSC2 Antibody (Center S1385/S1386)

APR10576G 0.1ml
EUR 580.8
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human TSC2 (Center S1385/S1386). This antibody is tested and proven to work in the following applications:

Polyclonal TSC2 Antibody (Center S1418/S1420)

APR10577G 0.1ml
EUR 580.8
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human TSC2 (Center S1418/S1420). This antibody is tested and proven to work in the following applications:

Polyclonal ERBB2 Antibody (C-term S1050/S1051)

APR04491G 0.1ml
EUR 580.8
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human ERBB2 (C-term S1050/S1051). This antibody is tested and proven to work in the following applications:

Phospho-RPS6KA1/RPS6KA3/RPS6KA2/RPS6KA6 (S221/227/S218/232) Antibody

1-CSB-PA040255
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  • 100ug
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Description: A polyclonal antibody against Phospho-RPS6KA1/RPS6KA3/RPS6KA2/RPS6KA6 (S221/227/S218/232). Recognizes Phospho-RPS6KA1/RPS6KA3/RPS6KA2/RPS6KA6 (S221/227/S218/232) from Human, Mouse. This antibody is Unconjugated. Tested in the following application: WB, ELISA;WB:1/500-1/2000.ELISA:1/40000

Nuclear Yellow [Hoechst S769121] *CAS 74681-68-8*

17539 25 mg
EUR 222

Nuclear Yellow [Hoechst S769121] *CAS 74681-68-8*

17539-25mg 25 mg
EUR 222
Description: The long-wavelength tracer nuclear yellow is often combined with the popular retrograde tracer true blue for two-color neuronal mapping.

Recombinant IAV H5N1 Hemagglutinin HA1 Subunit Protein (aa 1-341) [His] (A/Cambodia/S1211394/2008)

VAng-Wyb7155-100g 100 µg
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Description: Influenza A H5N1 (A/Cambodia/S1211394/2008) Hemagglutinin HA1 Subunit, recombinant protein.

Recombinant IAV H5N1 Hemagglutinin HA1 Subunit Protein (aa 1-341) [His] (A/Cambodia/S1211394/2008)

VAng-Wyb7155-10g 10 µg
EUR 687.6
Description: Influenza A H5N1 (A/Cambodia/S1211394/2008) Hemagglutinin HA1 Subunit, recombinant protein.

Recombinant IAV H5N1 Hemagglutinin HA1 Subunit Protein (aa 1-341) [His] (A/Cambodia/S1211394/2008)

VAng-Wyb7155-50g 50 µg
EUR 1330.8
Description: Influenza A H5N1 (A/Cambodia/S1211394/2008) Hemagglutinin HA1 Subunit, recombinant protein.

S0859

A3783-10 10 mg
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Description: S0859, an N-cyanosulphonamide compound, reversibly inhibited NBC-mediated pH(i) recovery (K (i)=1.7 microM, full inhibition at approximately 30 microM)

S0859

A3783-25 25 mg
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Description: S0859, an N-cyanosulphonamide compound, reversibly inhibited NBC-mediated pH(i) recovery (K (i)=1.7 microM, full inhibition at approximately 30 microM)

S0859

A3783-5 5 mg
EUR 193.2
Description: S0859, an N-cyanosulphonamide compound, reversibly inhibited NBC-mediated pH(i) recovery (K (i)=1.7 microM, full inhibition at approximately 30 microM)

S0859

9425-25 each
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S0859

9425-5 each
EUR 210

S3337

HY-U00222 5mg
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S119-8

HY-112543 10mM/1mL
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S0859

HY-15529 10mM/1mL
EUR 157.2

S-2474

HY-19212 20mg
EUR 7795.2

S-8921

HY-19298 10mg
EUR 6021.6

Monoclonal TRPC5 Antibody (clone S67-15), Clone: S67-15

APR10562G 0.05mg
EUR 580.8
Description: A Monoclonal antibody against Human TRPC5 (clone S67-15). The antibodies are raised in Mouse and are from clone S67-15. This antibody is applicable in WB and IHC-P, ICC

S100b/ Rat S100b ELISA Kit

ELI-02018r 96 Tests
EUR 1063.2

S100g/ Rat S100g ELISA Kit

ELI-15691r 96 Tests
EUR 1063.2

Monoclonal KCNB1 / Kv2.1 Antibody (clone S39-25), Clone: S39-25

AMM06068G 0.05mg
EUR 580.8
Description: A Monoclonal antibody against Human KCNB1 / Kv2.1 (clone S39-25). The antibodies are raised in Mouse and are from clone S39-25. This antibody is applicable in WB and IHC-P, ICC

Monoclonal KCNAB1 Antibody (clone S47-42), Clone: S47-42

AMM06080G 0.05mg
EUR 580.8
Description: A Monoclonal antibody against Human KCNAB1 (clone S47-42). The antibodies are raised in Mouse and are from clone S47-42. This antibody is applicable in WB and IHC-P, IP

Monoclonal GABRB3 Antibody (clone S87-25), Clone: S87-25

APR11975G 0.05mg
EUR 580.8
Description: A Monoclonal antibody against Human GABRB3 (clone S87-25). The antibodies are raised in Mouse and are from clone S87-25. This antibody is applicable in WB and IHC-P, IF, ICC

Monoclonal WASF1 / WAVE Antibody (clone S91-36), Clone: S91-36

APR10732G 0.05mg
EUR 580.8
Description: A Monoclonal antibody against Human WASF1 / WAVE (clone S91-36). The antibodies are raised in Mouse and are from clone S91-36. This antibody is applicable in WB and IHC-P, IP

S100B(S100B/1012) Antibody

BNC941012-100 100uL
EUR 238.8
Description: Primary antibody against S100B(S100B/1012), CF594 conjugate, Concentration: 0.1mg/mL

S100B(S100B/1012) Antibody

BNC941012-500 500uL
EUR 652.8
Description: Primary antibody against S100B(S100B/1012), CF594 conjugate, Concentration: 0.1mg/mL

S100B(S100B/1012) Antibody

BNC801012-100 100uL
EUR 238.8
Description: Primary antibody against S100B(S100B/1012), CF680 conjugate, Concentration: 0.1mg/mL

S100B(S100B/1012) Antibody

BNC801012-500 500uL
EUR 652.8
Description: Primary antibody against S100B(S100B/1012), CF680 conjugate, Concentration: 0.1mg/mL

S100B(S100B/1012) Antibody

BNC811012-100 100uL
EUR 238.8
Description: Primary antibody against S100B(S100B/1012), CF680R conjugate, Concentration: 0.1mg/mL

S100B(S100B/1012) Antibody

BNC811012-500 500uL
EUR 652.8
Description: Primary antibody against S100B(S100B/1012), CF680R conjugate, Concentration: 0.1mg/mL

S100B(S100B/1012) Antibody

BNC701012-100 100uL
EUR 238.8
Description: Primary antibody against S100B(S100B/1012), CF770 conjugate, Concentration: 0.1mg/mL

S100B(S100B/1012) Antibody

BNC701012-500 500uL
EUR 652.8
Description: Primary antibody against S100B(S100B/1012), CF770 conjugate, Concentration: 0.1mg/mL

S100B(S100B/1012) Antibody

BNC881012-100 100uL
EUR 238.8
Description: Primary antibody against S100B(S100B/1012), CF488A conjugate, Concentration: 0.1mg/mL

In this work, we show that the yeast starter Separase activate Cdk1 (Esp1 in yeast) through phosphorylation to trigger the onset of anaphase. Esp1 activation by a protein phosphatase 2A regulatory subunit associated with Cdc55 (PP2ACdc55) and Slk19 spindle protein.

Karina

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