TNF-alpha:TNFR1 binds DENN/MADD

Stable Identifier
Homo sapiens
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MAPK activating death domain (MADD) and DENN-SV are known to directly interact with TNFR1 cytoplasmic tail (Al-Zoubi AM et al. 2001). MADD and DENN-SV are two of at least six splice variants of IG20 gene. MADD and DENN-SV are constitutively expressed in all tissues and at much higher levels in cancer cells and tissues (Al-Zoubi AM et al. 2001; Lim KM et al. 2004). The expression of other IG20 isoforms, such as KIAA0358 and IG20-SV4, can be restricted to certain neuronal tissues (Li L et al. 2008). Regulation of expression of various splice variants can profoundly affect cancer cell survival, proliferation, or death (Efimova EV et al. 2004). Knockdown of IG20 using short hairpin RNA (shRNA) resulted in spontaneous apoptosis in HeLa (cervical cancer), PA-1 (ovarian carcinoma), WRO (follicular carcinoma) and FRO (anaplastic carcinoma) cells (Mulherkar N et al. 2006; Mulherkar N. et al. 2007; Subramanian M et al. 2009). MADD and DENN-SV have been shown to stimulate TNF-alpha and TRAIL-induced upregulation of prosurvival proteins suppressing caspase-8 activation (Kurada BR et al. 2009; Mulherkar N. et al. 2007; Subramanian M et al. 2009).

Literature References
PubMed ID Title Journal Year
16682944 MADD/DENN splice variant of the IG20 gene is necessary and sufficient for cancer cell survival

Mulherkar, N, Prabhakar, BS, Ramaswamy, M, Mordi, DC

Oncogene 2006
19289468 MADD, a splice variant of IG20, is indispensable for MAPK activation and protection against apoptosis upon tumor necrosis factor-alpha treatment

Li, LC, Subramanian, M, Prabhakar, BS, Prasad, KV, Mulherkar, N, Kurada, BR

J. Biol. Chem. 2009
14716293 IG20, in contrast to DENN-SV, (MADD splice variants) suppresses tumor cell survival, and enhances their susceptibility to apoptosis and cancer drugs

Lu, S, Prabhakar, BS, Efimova, EV, Al-Zoubi, AM, Martinez, O, Arima, T, Kaithamana, S

Oncogene 2004
11577081 Contrasting effects of IG20 and its splice isoforms, MADD and DENN-SV, on tumor necrosis factor alpha-induced apoptosis and activation of caspase-8 and -3

Efimova, EV, Prabhakar, BS, Dogan, RE, El-Idrissi, Mel-A, Kaithamana, S, Martinez, O, Al-Zoubi, AM

J. Biol. Chem. 2001
17314102 MADD/DENN splice variant of the IG20 gene is a negative regulator of caspase-8 activation. Knockdown enhances TRAIL-induced apoptosis of cancer cells

Prabhakar, BS, Prasad, KV, Mulherkar, N

J. Biol. Chem. 2007
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