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Definition

BAD is a member of the BCl-2 family of proteins and acts to promote apoptosis by forming heterodimers with the survival proteins BCL-2 and BCLXL, thus preventing them from binding with BAX1.  

 

Discovery

BAD was originally identified in a yeast two hybrid system that was used to screen for BCL-2 interacting proteins1.

 

Classification

BAD belongs to the BH3 sub-family of proteins that also includes other pro-apoptotic proteins; BH3 BID, BIK, BLK, HRK, BNIP3 and BIML2.

 

Structural Characteristics

BAD peptides contain a highly conserved alpha-helical BH3 domain through which they form heterodimers with BCL-2 and BCLXL3.  The BH3 domain is structurally defined as four-turn amphipathic a-helices, containing the sequence motif: Hy-X-X-X-Hy-X-X-X-Sm-D/E-X-Hy4.  This domain is sufficient for pro-apoptotic functions of BAD.

 

Mode of action

BAD peptides are located on the outer-mitochondrail membrane. Activation of NGF or IL-3 receptors on the mitochondrial membrane mediates the activation of AKT or PKA holoenzyme respectively that result in the phosphorylation of BAD at Ser-136 and 1122,5.  Phosphorylated BAD is translocated to the cytosol by phosphoserine binding protein. Following a death signal BAD is dephosporylated and found in association with BCL-XL-BCL-2 in which form BAD can exert its functions6.

 

Functions

BCL-2 family proteins that includes BAD play a pivotal role in deciding whether a cell will live or die by apoptosis.  Pro-apoptotic function of BAD is triggered by growth factor deprivation in the cell that results in its dephosphorylation and activation7. Activated BAD binds to BCL-2-BCL-XL and releases BAK and BAX that initiate apoptosis.  Increased BAD protein levels have been found in diseases like myocardial ischemia-reperfusion7.  BAD is also implicated in cancer. In mouse models it has been found that decrease in BAD levels leads to malignancy8.  Interestingly recent studies have shown that the tumor suppressor protein, p53 binds to BAD in response to DNA damage and in turn BAD triggers apoptosis of such cells thus maintaining cell physiology9.

 

 

References

 

1.     Elizabeth Y, Jiping Z, Jennifer J, Boise LH, Craig B, Thompson and Stanley JK, (1995). Bad, a heterodimeric partner for Bcl-xL and Bcl-2, displaces bax and promotes cell death. Cell, 80, Issue 2, 285-91.

2.     Atan G, James M.M, Stanley J.K (1999). BCL-2 family members and the mitochondria in apoptosis. Genes and Development, 13; 1899-1911.

3.     Sabine O, Jose-L D, William H, Julia C, Yan W, Gary W, Steve C, Suzanne W, Lawrence CF, and Tilman O (1997). Structural properties of Human BAD. J Biol. Chem., 372, 49, 30866-892.

4.     Beth L, Sangita S and Guido K (2008). Bcl-2 family members; Dual regulators of apoptosis and autophagy. Autophagy, 4:5, 600-606.

5.     Zha J, Harada H, Yang E, Jockel J, Kormeyer SJ (1996c). Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell87:619628.

6.     Zha J, Harada H, Osipov K, Jockel J, Waksman G, Korsmeyer SJ (1997). BH3 domain of BAD is required for heterodimerization with BCL-XL and pro-apoptotic activity. J. Biol. Chem.272:2410124104.

7.     Åsa BG and Roberta AG (2007). Bcl-2 family members and apoptosis, taken to heart. Am J Physiol Cell Physiol., 292:45-51.

8.     Zinkel S, Gross A and Yang E (2006). BCL2 family in DNA damage and cell cycle control. Cell Death and Differentiation, 13, 1351–1359.

9.     Peng J, Wenjing D and Mian W (2007). p53 and BAD: Remote strangers become close friends, Cell Research, 17: 283–285.

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If you are unable to find your desired product please contact us for assistance or send an email to info@biosyn.com

 
Product Name Catalog # Unit Price/Unit 
BAD (103 - 126), human
NLWAAQRYGRELRRMSDEFVDSFK
10470-01 1 mg $310 cart inquire
BAD (103 - 127), human
NLWAAQRYGRELRRMSDEFVDSFKK
10471-01 1 mg $198 cart inquire
Bad (103 - 127), human, all d - isomers
nlwaaqrygrelrrmsdefvdsfkk
10480-01 1 mg $370 cart inquire
BAD (103 - 127), human, FAM - labeled
FAM-NLWAAQRYGRELRRMSDEFVDSFKK
10472-01 1 mg $325 cart inquire
BAD (103 - 127), human, FAM - labeled -10472-005
FAM-NLWAAQRYGRELRRMSDEFVDSFKK
10472-005 0.5 mg $210 cart inquire
BAD (CT - 1)
KKGLPRPKSAGTATQMRQSSSWTC-CONH2
10476-01 1 mg $310 cart inquire
Bak-BH3, TAMRA-labeled
GQVGRQLAIIGDDINR-K(TAMRA)-CONH2
10473-005 0.5 mg $325 cart inquire
Bak-BH3 TAMRA-labeled
GQVGRQLAIIGDDINR-K(TAMRA)-CONH2
10473-01 0.1 mg $232 cart inquire
Bax BH3 peptide (55-74), wild type-10474-01
STKKLSECLKRIGDELDSNM
10474-01 1 mg $116 cart inquire
Bcl 9-2
GSEGLSKEQLEHRERSLQTLRDIERLLLRSGETEPFLKGPPGGAG-CONH2
10477-005 0.5 mg $330 cart inquire
BH3 BIM Peptide (52-71), human
Ac-MRPEIWIAQELRRIGDEFNA
10481-01 1 mg $250 cart inquire
BMf-BH3 (10478-01)
LQHRAEVQIARKLQCIADQFHRLHT
10478-01 1 mg $315 cart inquire
[Glu63] Bax BH3, mutant
STKKLSECEKRIGDELDSNM
10475-01 1 mg $250 cart inquire
Noxa BH3, Peptide 1
PAELEVECATQLRRFGDKLNFRQKLL
10479-01 1 mg $193 cart inquire

Biosynthesis Inc.