8
$\begingroup$

I am reading a paper about the regulation of the nuclear export of the protein GSK3 and I have come across the following statement:

Full-length FLAG epitope-tagged mFrat1 (FLAG-Frat) and the amino-terminal half of Frat (ΔC Frat) localized predominantly to the cytoplasm of transfected MDCK cells (Fig. 1, A and B, i and iii). Unexpectedly, the carboxyl-terminal half of Frat (ΔN Frat) accumulated preferentially in the nuclei of transfected cells (Fig. 1B, iv).

I am not sure why the amino-terminal and carboxyl-terminal half of the Frat protein are referred to as ΔC Frat and ΔN Frat respectively. I know that the amino terminus of a protein is also referred to as the N-terminus, whilst the carboxyl terminus of a protein is referred to as the C-terminus. I am not sure why in this paper ΔC and ΔN are used to refer to the amino-terminal and carboxyl-terminal half of the Frat protein.

Any insights are appreciated.

$\endgroup$
1
  • $\begingroup$ This is just a simple technical abbreviation. Δ is used to mean deletion, so ΔC is used for the N-terminal fragment as the C-terminal part has been deleted. One shouldn’t write answers in comments, but this doesn’t need any more. $\endgroup$ – David Jan 21 at 19:12
10
$\begingroup$

The Frat/GBP (frequently rearranged in T-cell lymphomas/GSK-3-binding protein) protein is a proto-oncogene that regulates the Wnt signalling pathway. (van Amerongen et al., 2004)

The cited paper (Franca-Koh, 2002) noted a correlation between some forms of Frat and GSK3 cellular localization. Without Frat, GSK3 is cytoplasmic. In the presence of Frat, the heterodimer Frat-GSK3 translocates to the nucleus. As Frat is phosphorylated, it was unclear then what mechanism(s) was(were) involved. To investigate the role of Frat, the authors hypothesized that a region of Frat may be involved, not necessarily the whole protein.

They engineered deletion constructs and added an N-terminal FLAG tag for easy affinity purification. They used the symbol delta (Δ) for deletion. The N-terminal region of residues 1 – 129 encompassing Domain 1, i.e. deletion of the C-terminal region is called ΔC; likewise, the C-terminal region of residues 129-274 encompassing Domain 2, i.e. deletion of the N-terminus is called ΔN. They also engineered a green fluorescent protein (GFP) tag fusion protein variant. Here are their constructs as illustrated on Figure 1 of their paper:

Molecules

Human ortholog
I aligned the residue sequence of the murine Frat with the human orthologs: it has 79% identity to human Frat1 and 68% identity to human Frat2. mFrat residues 1 – 129 (ΔC) and 129 – 274 (ΔN) correspond to hFrat1 residues 1 – 132 and 132 – 279, respectively.

Added Note
Here is a co-crystal structure of GSK3β (N-terminal lobe in orange and C-terminal lobe in cyan) complexed with Frat1 peptide 197-226 (forest green) and an inhibitor (N-(6-(3,4-dihydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)acetamide) (green) as deposited with RCSB as entry 5OY4.pdb . The presence of the inhibitor helps locate the active site in the image of the GSK3b protein kinase.
Molecules

References
Franca-Koh, J., Yeo, M., Fraser, E., Young, N. and Dale, T.C. (2002) J. Biol. Chem. 277:43844-43848.

Van Amerongen, R., van der Gulfen, H., Bleeker, F., Jonkers, J. and Berns, A. (2004) J. Biol. Chem. 279:26967-26974.

$\endgroup$

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.