Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

Pubmed ID :26658105
Publication Date : //

Molecular evidence of Zn chelation of the procaspase activating compound B-PAC-1 in B cell lymphoma.


The resistance of apoptosis in cancer cells is pivotal for their survival and is typically ruled by mutations or dysregulation of core apoptotic cascade. Mantle cell lymphoma (MCL) is a non-Hodgkin's B-cell malignancy expressing higher anti-apoptotic proteins providing survival advantage. B-PAC-1, a procaspase activating compound, induces apoptosis by sequestering Zn bound to procaspase-3, but the amino acids holding Zn in Caspase-3 is not known. Here we show that reintroduction of WT caspase-3 or 7 in Caspase3-7 double knock-out (DKO) mouse embryonic fibroblasts (MEF) promoted B-PAC-1 to induce apoptosis (27-43%), but not in DKO MEFs or MEFs expressing respective Casp3-7 catalytic mutants (12-13%). Using caspase-6 and -9 exosite analysis, we identified and mutated predicted Zn-ligands in caspase-3 (H108A, C148S and E272A) and overexpressed into DKO MEFs. Mutants carrying E272A abrogated Zn-reversal of apoptosis induced by B-PAC-1 via higher XIAP and smac expressions but not in H108A or C148S mutants. Co-immunoprecipitation analysis revealed stronger XIAP-caspase-3 interaction suggesting a novel mechanism of impulsive apoptosis resistance by disrupting predicted Zn-ligands in caspase-3. B-PAC-1 sponsored apoptosis in MCL cell lines (30-73%) via caspase-3 and PARP cleavages accompanied by loss of Mcl-1 and IAPs including XIAP while Zn substantially abrogated B-PAC-1-driven apoptosis (18-36%). In contrary, Zn is dispensable to inhibit staurosporin, bendamustine, ABT199 or MK206-induced apoptosis. Consistent to cell lines, B-PAC-1 stimulated cell death in primary B-lymphoma cells via caspase-3 cleavage with decline in both Mcl-1 and XIAP. This study underscores the first genetic evidence that B-PAC-1 driven apoptosis is mediated via Zn chelation.

Authors : Sarkar Aloke , Balakrishnan Kumudha , Chen Jefferson , Patel Viralkumar , Neelapu Sattva S , McMurray John S , Gandhi Varsha ,

Related products :

Catalog number Product name Quantity
'CS20-00-003 Human Lymphoma tissue array (Plasmacytic lymphoma B-cell Large B-cell Burkitts lymphoma T-lymphoblastoma, etc.) tissues 7 x 9
'CS20-00-002 Human Lymphoma tissue array (Diffuse large cell B-cell T-cell Hodgkin lymphoma follicular diffuse B-cell, etc.) tissues 7 x 9
LF-PA0178 anti-Bcl-2(B cell lymphoma 2), Rabbit polyclonal to Bcl-2(B cell lymphoma 2), Isotype IgG, Host Rabbit 100 ul
orb80956 Human B-Cell Lymphoma Protein Alpha His tag protein Bcl2 Human Recombinant produced in E.coli is a single, non-glycosylated polypeptide chain containing amino acids 1-211 and having a molecular mass o 5
26-970 Functions of the cell cortex, including motility, adhesion, and cytokinesis, are mediated by the reorganization of the actin cytoskeleton and recent evidence suggests a role for the Formin homology (F 0.05 mg
Lymphoma - LYM761 Lymphoma array, 75 cases of various types of nodal and extranodal lymphoma, together with LYM321, LYM401 and LYM771 forming the lymphoma array set. 1.1mm
Lymphoma - LYM401 Lymphoma array, 39 cases of various types of nodal and extranodal lymphoma, together with LYM321, LYM761 and LYM771 forming the lymphoma array set. 1.1mm
Lymphoma - LYM321 Lymphoma array, 32 cases of various types of nodal and extranodal lymphoma, together with LYM401, LYM761 and LYM771 forming the lymphoma array set. 1.5mm
Lymphoma - LYM771 Lymphoma array, 75 cases of various types of nodal and extranodal lymphoma, together with LYM321, LYM401 and LYM761 forming the lymphoma array set. 1.1mm
10-002-38043 NCR. NKp46 (Extracellular Ig-like domain. 22-255aa. human) - Natural Killer (NK) Cell Activating Receptor NKp46; Natural killer cell p46-related protein; NKp46; hNKp46; NK-p46; NK cell-activating rece 0.1 mg
10-002-38043 NCR. NKp46 (Extracellular Ig-like domain. 22-255aa. human) - Natural Killer (NK) Cell Activating Receptor NKp46; Natural killer cell p46-related protein; NKp46; hNKp46; NK-p46; NK cell-activating rece 0.5 mg
Lymphoma - LYM1501 Lymphoma array, 70 cases of various types of nodal and extranodal lymphoma all in duplicates together with 5 cases of non_malignant lymphoid tissues 1.1 mm
EIAAB41327 FKSG15,Homo sapiens,Human,TAGAP,TAGAP1,T-cell activation GTPase-activating protein,T-cell activation Rho GTPase-activating protein
27-497 CGI-143 encodes proteins that seem to be involved in cell proliferation or cell-cycle regulation, but the molecular function is still unknown. 0.05 mg
EIAAB41326 Mouse,Mus musculus,Tagap,T-cell activation GTPase-activating protein,T-cell activation Rho GTPase-activating protein
orb60876 Fisetin Fisetin(Fustel) is a potent sirtuin activating compound (STAC) and an agent that modulates sirtuins. For research use only. 10 mg
RPR-460 Recombinant Human B-cell CLL lymphoma 6 2
RPR-318 Recombinant Human B-cell CLL lymphoma 7A 2
LF-PA0178 anti-Bcl-2 (B cell lymphoma 2) 100 ul
LF-PA0178 anti_Bcl_2(B cell lymphoma 2) 100 ul
RPR-058 Recombinant Human B-cell CLL Lymphoma 10 1
pro-460 Recombinant Human B-cell CLL per lymphoma 6 5
pro-460 Recombinant Human B-cell CLL per lymphoma 6 10
pro-460 Recombinant Human B-cell CLL per lymphoma 6 2
E02B0574 Rat B-Cell CLL Lymphoma 10 ELISA 96T/kit


 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur | Gentaur





GENTAUR Ltd.
Unicorn House, Station Cl
Hertfordshire, Potters Bar EN6 1TL
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017
RIB 30004 00187 00010092253 10
BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG
IBAN FR76 3000 4001 8700 0100 9225 310
france@gentaur.com | Gentaur | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: +49 0241 40 08 90 86, +49 0241 95 78 94 78, +49 0241 40 08 90 86
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur | Gentaur