DFFA Research Reagents

DNA fragmentation factor subunit alpha is a protein in humans that is encoded by DFFA gene. Inhibitor of the caspase-activated DNase (DFF40).

The following DFFA reagents supplied by CUSABIO are manufactured under a strict quality control system. Multiple applications have been validated and solid technical support is offered.

DFFA Antibodies

DFFA Antibodies for Homo sapiens (Human)

DFFA Proteins

DFFA Proteins for Homo sapiens (Human)

DFFA Proteins for Mus musculus (Mouse)

DFFA Background

DNA fragmentation factor subunit alpha (DFFA) is one of the two subunits of the heterodimeric protein DNA Fragmentation Factor (DFF), a major endonuclease responsible for chromosomal DNA cleavage during apoptosis [1]. It is also called DNA fragmentation factor 45 kDa subunit (DFF45) because its molecular weight is 45 kDa. DFF45 is indispensable for the expression and folding of DFF40, thus acting as a molecular chaperone [1][5]. In non-apoptotic cells, DFF45 exists as a heterodimeric complex with DFF40. Upon activation of apoptosis, DFF45 is cleaved by caspase 3 and then dissociates from DFF40, another subunit of the DFF [1][3]. Removal of DFF45 releases and activates DFF40 [2][3]. In other words, DFF45 suppresses the activity of DFF40, a caspase-activated DNase, or nuclease (CAD or CPAN) [4]. So DFF45 is named the inhibitor of the caspase-activated DNase (ICAD), too. Active DFF40 is capable of cleaving chromosomal DNA into oligonucleosomal size fragments [5]. The biochemical hallmark of apoptosis is the cleavage of chromatin into nucleosomal fragments [6]. Studies showed that caspase 7 and granzyme B can also process DFF45 during apoptosis [2][7]. DFF35 (or ICAD-S), a short form of DFF45, lacks C-terminus and consists of amino acids 1-65 of DFF45, and is produced by alternative splicing and is expressed in numerous different cells [8][9][10]. DFF35/ICAD-S also inhibits DFF40/CAD activity but lacks the chaperon function [11][12]. Decreased DFF45 expression has been observed in renal, colorectal, and esophageal cancers. It has been postulated that the downregulation of DFF45 may play a role in tumor escape from apoptosis and may promote tumor progression and metastasis [13][14][15].

[1] Liu X, Zou H, et al. DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis [J]. Cell 1997; 89:175-4.
[2] Liu X, Zou H, et al. Activation of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease) [J]. J Biol Chem 1999; 74:13836-0.
[3] Sakahira H, Enari M, et al. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis [J]. Nature 1998; 391:96-9.
[4] Halenbeck R, MacDonald H, et al. CPAN, a human nuclease regulated by the caspase-sensitive inhibitor DFF45 [J]. Curr Biol 1998; 8:537-0.
[5] Liu X, Li P, et al. DFF40 induces DNA fragmentation and chromatin condensation during apoptosis [J]. Proc Natl Acad Sci USA 1998; 95:8461-8466.
[6] A.H Wyllie Glucocorticoid induced thymocyte apoptosis is associated with endogeneous endonuclease activation [J]. Nature, 284 (1980), pp. 555-556.
[7] Thomas D, Du C, et al. DFF45/ICAD can be directly process by granzyme B during the induction of apoptosis [J]. Immunity 2000; 12:621-2.
[8] M Enari, H Sakahira, et al. A Caspase-Activated DNase That Degrades DNA During Apoptosis, and Its Inhibitor ICAD [J]. Nature, 1998, 391 (6662), 43-50.
[9] Sabol, S.L., et al. Inhibition of apoptosis-associated DNA fragmentation activity in nonapoptotic cells: the role of DNA fragmentation factor-45(DFF45/ICAD) [J]. Biochem. Biophys. Res. Commun. 1998, 253: 151-58.
[10] Kawane, K., H. Fukuyama, et al. Structure and promoter analysis of murine CAD and ICAD genes [J]. Cell Death Differ. 1999, 6: 745-52.
[11] Gu, J., R.P. Dong, et al. Functional interaction of DFF35 and DFF45 with caspase-activated DNA fragmentation nuclease DFF40 [J]. J. Biol. Chem. 1999, 274: 20759-0762.
[12] Sakahira, H., M. Enari, et al. Functional differences of two forms of the inhibitor of caspase-activated DNase, ICAD-L and ICAD-S [J]. J. Biol. Chem. 1999, 274: 15740-5744.
[13] Rajandram R, Razack AH, et al. Decreased Expression of Inhibitor of Caspase-Activated DNase (ICAD) in Renal Cell Carcinoma - Tissue Microarray of Human Samples [J]. J Kidney Cancer VHL. 2016; 3(1):1-11.
[14] Konishi S, Ishiguro H, Shibata Y, et al. Decreased expression of DFF45/ICAD is correlated with a poor prognosis in patients with esophageal carcinoma. Cancer. 2002;95(12):2473-478.
[15] Errami Y, Brim H, Oumouna-Benachour K, et al. ICAD deficiency in human colon cancer and predisposition to colon tumorigenesis: linkage to apoptosis resistance and genomic instability. PLoS One. 2013;8(2):e57871.

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