Taxonomic distribution of proteins containing LITAF domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing LITAF domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4.

Jolliffe CN, Harvey KF, Haines BP, Parasivam G, Kumar S
Biochem J. 2000; 351: 557-65

Nedd4 is a member of a growing family of ubiquitin-protein ligases which consist of a lipid-binding domain, two to four WW domains and a C-terminal ubiquitin-protein ligase domain. The Nedd4 mRNA levels are developmentally regulated and Nedd4 protein is highly expressed in many mouse embryonic tissues. In this study we have used a far-Western screen to identify embryonic proteins that interact with the WW domains in mouse Nedd4. We report here identification of eight Nedd4 WW-domain-interacting proteins from mouse embryonic cDNA expression libraries. Two of the proteins are novel, while two have been identified previously as ligands for a WW domain. All of these proteins contain one or more PY motifs. In seven of the eight proteins, these PY motifs are necessary for their interaction with the WW domains of Nedd4. Using site-directed mutagenesis, and by using individual WW domains of Nedd4 as probes for far-Western analysis, we show that the three WW domains in Nedd4 interact with varying affinities with the PY motifs present in various Nedd4-binding proteins. These results provide evidence that Nedd4 can potentially interact with multiple proteins, possibly simultaneously, through its WW domains.

A novel lipopolysaccharide-induced transcription factor regulating tumornecrosis factor alpha gene expression: molecular cloning, sequencing,characterization, and chromosomal assignment.

Myokai F, Takashiba S, Lebo R, Amar S
Proc Natl Acad Sci U S A. 1999; 96: 4518-23

Lipopolysaccharide (LPS) is a potent stimulator of monocytes andmacrophages, causing secretion of tumor necrosis factor alpha (TNF-alpha)and other inflammatory mediators. Given the deleterious effects to thehost of TNF-alpha, it has been postulated that TNF-alpha gene expressionmust be tightly regulated. The nature of the nuclear factor(s) thatcontrol TNF-alpha gene transcription in humans remains obscure, althoughNF-kappaB has been suggested. Our previous studies pertaining tomacrophage response to LPS identified a novel DNA-binding domain locatedfrom -550 to -487 in the human TNF-alpha promoter that containstranscriptional activity, but lacks any known NF-kappaB-binding sites. Wehave used this DNA fragment to isolate and purify a 60-kDa protein bindingto this fragment and obtained its amino-terminal sequence, which was usedto design degenerate probes to screen a cDNA library from THP-1 cells. Anovel cDNA clone (1.8 kb) was isolated and fully sequenced.Characterization of this cDNA clone revealed that its induction wasdependent on LPS activation of THP-1 cells; hence, the name LPS-inducedTNF-alpha factor (LITAF). Inhibition of LITAF mRNA expression in THP-1cells resulted in a reduction of TNF-alpha transcripts. In addition, highlevel of expression of LITAF mRNA was observed predominantly in theplacenta, peripheral blood leukocytes, lymph nodes, and the spleen.Finally, chromosomal localization using fluorescence in situ hybridizationrevealed that LITAF mapped to chromosome 16p12-16p13.3. Together, thesefindings suggest that LITAF plays an important role in the activation ofthe human TNF-alpha gene and proposes a new mechanism to control TNF-alphagene expression.