Testin
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Testin (also known as TESS) is a
Domain organisation
Tes is composed of the following domains:
Domain Name | Boundaries | Domain type |
---|---|---|
Cysteine rich domain | 1–90 | No Homology |
PET domain | 90–200 | PET domain – no structure |
Linker . | 201–233 | no domain |
LIM1 | 234–300 | LIM domain |
LIM2 | 300–365 | LIM domain |
LIM3 | 366–421 | LIM domain |
The structures of the Cysteine rich domain and the PET domain are not known. LIM domains, however, are known as modulators of protein interactions.
Binding partners
TES does not appear to be an
reveal that TES has putative interactions mediated by the indicated domain:Partner | Domain | ref | Method |
---|---|---|---|
mENA/VASP | LIM3 | [6][9][10] | ITC
|
Arp7a | ??? | [6] | Yeast two Hybrid |
Zyxin | LIM1 | [6][9] | Yeast two Hybrid, Pull-down assay |
Actin | PET? | [9] | Pull-down assay |
α-Actinin | PET? | [9] | Pull-down assay |
Paxillin | PET? | [9] | Pull-down assay |
Garvalov et al. showed that the interaction between TES & zyxin were direct, using recombinant proteins expressed in E. coli.[9]
Some of the potential binding partners (Zyxin, mENA) can be found in focal adhesion complexes; the range of binding partners indicates a potential role for TES in-between 'privileged' Actin polymerisation and focal adhesion contacts to the extracellular matrix. This tallies with the observation that GFP-tagged TES can be seen at focal adhesions.
TES as a tumour suppressor
In December 2007, Boeda, Briggs et al.
These finding were significant given that Mena is often over-expressed in cancer cells, and is thought to be partly responsible for cancer cell motility, and therefore a factor in cancer metastasis. TES is conversely often not produced in cancer cells. It is possible that a drug designed to mimic TES's interaction with Mena could be used to prevent metastasis and thus development of secondary tumours in cancer patients. The work was widely reported in the British press (the work was carried out by Cancer Research UK),[11][12][13] and also in the international press.[14][15]
Conformational change
Based on the observations that:[citation needed]
- Mammalian cell derived TES binding Zyxin
- E. coli-produced recombinant TES (rTES) does not bind Zyxin
- An rTES construct composed of residues 201–421 (i.e., the linker and all 3 LIM domains) does bind Zyxin
- The above rTES construct binds an N-terminal rTES construct, consisting of the cysteine rich and PET domains – IE, the two-halves of TES interact with each other.
Garvalov et al. propose that TES exists in two conformational states: A 'closed' state where the N & C halves of TES interact, obscuring the Zyxin binding site in LIM1, and an 'open' state where the Zyxin binding site is accessible and the two halves no-longer interact in the same fashion, if at all. The regulatory mechanism switching between the two states is not presently fully understood.
Phenotype
In
In gene knockout experiments,
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000135269 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029552 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 10950921.
- ^ S2CID 26602119.
- PMID 16033868.
- PMID 9594664.
- ^ PMID 12695497.
- ^ PMID 18158903.
- ^ "Drug target to stop cancer spread". BBC News. 6 October 2010. Retrieved 6 October 2010.
- ^ Jha A (28 December 2007). "New light shed on how cancers spread". Science. The Guardian. Retrieved 6 October 2010.
- ^ Fletcher V (28 December 2007). "The Cancer 'Life Saver'". UK News. Express.co.uk. Retrieved 6 October 2010.
- ^ "Cancer's spreading mechanism found". Science. The Sydney Morning Herald. 29 December 2007. Retrieved 6 October 2010.
- ^ "Clue found to checking cancer spread". The Times of India. 29 December 2007. Archived from the original on 19 October 2012. Retrieved 6 October 2010.