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TRAF4, at the Crossroad between Morphogenesis and Cancer.

Rousseau A, Rio MC, Alpy F - Cancers (Basel) (2011)

Bottom Line: TRAF4 encodes an adaptor protein that belongs to the TRAF protein family.While most TRAF proteins influence immune and inflammation processes, TRAF4 is mainly involved in developmental and morphogenic processes.Interestingly, this protein has been shown to be linked to crucial cellular functions such as cell polarity and the regulation of reactive oxygen species production.

View Article: PubMed Central - PubMed

Affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), UMR 7104 CNRS, U964 INSERM, Université de Strasbourg, BP 10142, 67404 Illkirch, C.U. de Strasbourg, France. fabien.alpy@igbmc.fr.

ABSTRACT
Tumor Necrosis Factor Receptor-Associated Factor 4 (TRAF4) is a gene whose expression is altered in cancers. It is overexpressed in a variety of carcinomas of different origins, often as a consequence of amplification. TRAF4 encodes an adaptor protein that belongs to the TRAF protein family. While most TRAF proteins influence immune and inflammation processes, TRAF4 is mainly involved in developmental and morphogenic processes. Interestingly, this protein has been shown to be linked to crucial cellular functions such as cell polarity and the regulation of reactive oxygen species production.

No MeSH data available.


Related in: MedlinePlus

Modular organization of the human TRAF4 protein. (a) TRAF4 is a 470 amino acid protein, harboring conserved RING, Zinc Finger (ZF1-ZF7) and TRAF domains. (b) Cartoon diagram of the nuclear magnetic resonance (NMR) solution structure of TRAF4 zinc finger motif 5 (PDB ID : 2EOD). Residues interacting with the zinc atom (red) are represented by green sticks. (c) Alignment of the zinc finger containing region of TRAF proteins performed with the ClustalX software [27]. Identical residues in all sequences are shown by an asterisk. Amino acids interacting with zinc atoms are highlighted in green. Residues corresponding to the sequence shown in panel b are in bold type.
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f1-cancers-03-02734: Modular organization of the human TRAF4 protein. (a) TRAF4 is a 470 amino acid protein, harboring conserved RING, Zinc Finger (ZF1-ZF7) and TRAF domains. (b) Cartoon diagram of the nuclear magnetic resonance (NMR) solution structure of TRAF4 zinc finger motif 5 (PDB ID : 2EOD). Residues interacting with the zinc atom (red) are represented by green sticks. (c) Alignment of the zinc finger containing region of TRAF proteins performed with the ClustalX software [27]. Identical residues in all sequences are shown by an asterisk. Amino acids interacting with zinc atoms are highlighted in green. Residues corresponding to the sequence shown in panel b are in bold type.

Mentions: The TRAF protein family is composed of seven members that share a common structural organization (Figure 1) [2,6,8-10]. All TRAF proteins contain a C-terminal TRAF domain except TRAF7 where this domain is substituted by seven WD40 repeats [11,12]. The TRAF domain, which is involved in the homo- and heterotrimerization of TRAF proteins is mushroom-like in shape with a stalk-like N-TRAF and a cap-like C-TRAF [11,13-16]. The N-TRAF domain forms a trimeric parallel coiled-coil conformation [11]; in TRAF4, this region is short compared with other TRAF family members as it contains only 3 heptads while other TRAF proteins contain more than 10 heptads [4]. This difference might explain the poor ability of TRAF4 to associate with other TRAF proteins [17]. The C-TRAF domain forms an eight-stranded β-sandwich, a fold that is not restricted to TRAF proteins. Indeed, this domain is also known as the meprin and TRAF-C homology (MATH) domain because of its sequence homology with the meprin extracellular metalloprotease family [18-20]. The C-TRAF domain is involved in the trimerization of TRAF proteins. Moreover, it serves as the docking site of upstream partners during signaling by interacting directly with membrane receptors or indirectly with proteins attached to these receptors. For instance, key surface residues of the TRAF2 C-TRAF domain are involved in its interaction with the TNF receptor superfamily member, TNFR2 [14]. The N-TRAF domain is also involved in protein-protein interactions such as in TRAF2 where it is the binding site for the E3-ligase c-IAP2 [21].


TRAF4, at the Crossroad between Morphogenesis and Cancer.

Rousseau A, Rio MC, Alpy F - Cancers (Basel) (2011)

Modular organization of the human TRAF4 protein. (a) TRAF4 is a 470 amino acid protein, harboring conserved RING, Zinc Finger (ZF1-ZF7) and TRAF domains. (b) Cartoon diagram of the nuclear magnetic resonance (NMR) solution structure of TRAF4 zinc finger motif 5 (PDB ID : 2EOD). Residues interacting with the zinc atom (red) are represented by green sticks. (c) Alignment of the zinc finger containing region of TRAF proteins performed with the ClustalX software [27]. Identical residues in all sequences are shown by an asterisk. Amino acids interacting with zinc atoms are highlighted in green. Residues corresponding to the sequence shown in panel b are in bold type.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757440&req=5

f1-cancers-03-02734: Modular organization of the human TRAF4 protein. (a) TRAF4 is a 470 amino acid protein, harboring conserved RING, Zinc Finger (ZF1-ZF7) and TRAF domains. (b) Cartoon diagram of the nuclear magnetic resonance (NMR) solution structure of TRAF4 zinc finger motif 5 (PDB ID : 2EOD). Residues interacting with the zinc atom (red) are represented by green sticks. (c) Alignment of the zinc finger containing region of TRAF proteins performed with the ClustalX software [27]. Identical residues in all sequences are shown by an asterisk. Amino acids interacting with zinc atoms are highlighted in green. Residues corresponding to the sequence shown in panel b are in bold type.
Mentions: The TRAF protein family is composed of seven members that share a common structural organization (Figure 1) [2,6,8-10]. All TRAF proteins contain a C-terminal TRAF domain except TRAF7 where this domain is substituted by seven WD40 repeats [11,12]. The TRAF domain, which is involved in the homo- and heterotrimerization of TRAF proteins is mushroom-like in shape with a stalk-like N-TRAF and a cap-like C-TRAF [11,13-16]. The N-TRAF domain forms a trimeric parallel coiled-coil conformation [11]; in TRAF4, this region is short compared with other TRAF family members as it contains only 3 heptads while other TRAF proteins contain more than 10 heptads [4]. This difference might explain the poor ability of TRAF4 to associate with other TRAF proteins [17]. The C-TRAF domain forms an eight-stranded β-sandwich, a fold that is not restricted to TRAF proteins. Indeed, this domain is also known as the meprin and TRAF-C homology (MATH) domain because of its sequence homology with the meprin extracellular metalloprotease family [18-20]. The C-TRAF domain is involved in the trimerization of TRAF proteins. Moreover, it serves as the docking site of upstream partners during signaling by interacting directly with membrane receptors or indirectly with proteins attached to these receptors. For instance, key surface residues of the TRAF2 C-TRAF domain are involved in its interaction with the TNF receptor superfamily member, TNFR2 [14]. The N-TRAF domain is also involved in protein-protein interactions such as in TRAF2 where it is the binding site for the E3-ligase c-IAP2 [21].

Bottom Line: TRAF4 encodes an adaptor protein that belongs to the TRAF protein family.While most TRAF proteins influence immune and inflammation processes, TRAF4 is mainly involved in developmental and morphogenic processes.Interestingly, this protein has been shown to be linked to crucial cellular functions such as cell polarity and the regulation of reactive oxygen species production.

View Article: PubMed Central - PubMed

Affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), UMR 7104 CNRS, U964 INSERM, Université de Strasbourg, BP 10142, 67404 Illkirch, C.U. de Strasbourg, France. fabien.alpy@igbmc.fr.

ABSTRACT
Tumor Necrosis Factor Receptor-Associated Factor 4 (TRAF4) is a gene whose expression is altered in cancers. It is overexpressed in a variety of carcinomas of different origins, often as a consequence of amplification. TRAF4 encodes an adaptor protein that belongs to the TRAF protein family. While most TRAF proteins influence immune and inflammation processes, TRAF4 is mainly involved in developmental and morphogenic processes. Interestingly, this protein has been shown to be linked to crucial cellular functions such as cell polarity and the regulation of reactive oxygen species production.

No MeSH data available.


Related in: MedlinePlus