Biology:Translationally controlled tumour protein
| TCTP | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 translationally controlled tumor-associated protein p23fyp from schizosaccharomyces pombe | |||||||||
| Identifiers | |||||||||
| Symbol | TCTP | ||||||||
| Pfam | PF00838 | ||||||||
| Pfam clan | CL0080 | ||||||||
| InterPro | IPR018105 | ||||||||
| PROSITE | PDOC00768 | ||||||||
| SCOP2 | 1h7y / SCOPe / SUPFAM | ||||||||
| |||||||||
| Translationally Controlled Tumour Protein | |
|---|---|
| Identifiers | |
| Symbol | FLJ27337,tpt1,HRF, p02, p23, p21 |
| OMIM | 600763 |
The translationally controlled tumour protein, commonly known as TCTP, is a highly conserved protein among many eukaryotic organisms.[1] TCTP is involved in a variety of cellular activities, including microtubule stabilization, calcium-binding activities, and apoptosis.[1] The Mammalian translationally controlled tumour protein (TCTP) (or P23) is a protein which has been found to be preferentially synthesised in cells during the early growth phase of some types of tumour,[2][3] but which is also expressed in normal cells. It was first identified as a histamine-releasing factor, acting in IgE +-dependent allergic reactions. In addition, TCTP has been shown to bind to tubulin in the cytoskeleton, has a high affinity for calcium, is the binding target for the antimalarial compound artemisinin, and is induced in vitamin D-dependent apoptosis. TCTP production is thought to be controlled at the translational as well as the transcriptional level.[4]
Conservation
TCTP is a hydrophilic protein of 18 to 20 kD. TCTPs do not share significant sequence similarity with any other class of proteins. Recently, the structure of TCTP was determined and exhibited significant structural similarity to the human protein Mss4, which is a guanine nucleotide-free chaperone of the Rab protein.[5] Translationally controlled tumor protein (TCTP) is a highly conserved protein found in eukaryotes, across animal and plant kingdoms and even in yeast. Close homologues have been found in plants,[6] earthworm,[7] Caenorhabditis elegans (F52H2.11), Hydra, Saccharomyces cerevisiae (YKL056c),[8] Schizosaccharomyces pombe (SpAC1F12.02c) and protozoa like Trypanosoma brucei.[9][10] Mammalian TCTP is ubiquitously expressed in various tissues and cell types.
Function
Translationally-controlled tumor-associated protein (TCTP) has many roles in cellular processes, most notably in the following:
- cancer,
- embryo development, specifically axon growth and guidance,[11]
- cell cycle,
- apoptosis,
- Cell proliferation,
- growth,
- tumor reversion,
- stress response,
- gene regulation,
- heat shock
In essence, TCTP functions as molecule that prevents cell death. It reduces cellular stress working as a heat shock protein and a molecular chaperone. It prevents cell death by binding to calcium, an ion that causes cell death. Furthermore, the N-terminal domain of TCTP inhibits apoptosis by binding to apoptotic factors and by inhibiting p53 tumour suppressor-dependent apoptosis by downregulating it.[12]
TCTP interacts with F-actin and mitotic spindle [13] and regulates cell shape by interacting with the cytoskeleton. Since most cellular processes, such as the cell cycle and cancer, involve changes in the cytoskeleton; it becomes apparent why TCTP is important. Moreover, if the gene encoding TCTP is knocked-out in mice, it becomes embryonic lethal, and they die in utero (in the womb).[14]
Translationally Controlled Tumor Protein (TCTP/tpt1) is a regulator of the cancer stem cell compartment,[15] the tumor reversion program,[16][17] tumor progression and certain forms of inflammatory diseases.[18] Susini L et al. described TCTP as a pro-survival protein by antagonizing BAX function [19]
Structure
This structure has a very complex topology composed of four beta-sheets and three alpha helices.[5]
Interactions
TCTP has been shown to interact with:
TCTP is reported to interact with dozens of other proteins, which relates to its functions in many cellular and physiological processes.[22]
References
- ↑ 1.0 1.1 "The translationally controlled tumour protein (TCTP)". The International Journal of Biochemistry & Cell Biology 36 (3): 379–385. March 2004. doi:10.1016/S1357-2725(03)00213-9. PMID 14687915.
- ↑ "The growth-related protein P23 of the Ehrlich ascites tumor: translational control, cloning and primary structure". Biochemistry International 19 (2): 277–286. August 1989. PMID 2479380.
- ↑ "Nucleotide sequence of a major messenger RNA for a 21 kilodalton polypeptide that is under translational control in mouse tumor cells". Nucleic Acids Research 16 (5): 2350. March 1988. doi:10.1093/nar/16.5.2350. PMID 3357792.
- ↑ "Expression of the gene and processed pseudogenes encoding the human and rabbit translationally controlled tumour protein (TCTP)". European Journal of Biochemistry 267 (17): 5473–5481. September 2000. doi:10.1046/j.1432-1327.2000.01609.x. PMID 10951206.
- ↑ 5.0 5.1 "Structure of TCTP reveals unexpected relationship with guanine nucleotide-free chaperones". Nature Structural Biology 8 (8): 701–704. August 2001. doi:10.1038/90415. PMID 11473261.
- ↑ "An alfalfa cDNA encodes a protein with homology to translationally controlled human tumor protein". Plant Molecular Biology 19 (3): 501–503. June 1992. doi:10.1007/bf00023399. PMID 1623194.
- ↑ "Identification of heavy metal induced changes in the expression patterns of the translationally controlled tumour protein (TCTP) in the earthworm Lumbricus rubellus1". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1398 (3): 294–304. July 1998. doi:10.1016/s0167-4781(98)00077-3. PMID 9655922.
- ↑ "Sequence of a 28.6 kb region of yeast chromosome XI includes the FBA1 and TOA2 genes, an open reading frame (ORF) similar to a translationally controlled tumour protein, one ORF containing motifs also found in plant storage proteins and 13 ORFs with weak or no homology to known proteins". Yeast 10 Suppl A: S63–S68. April 1994. doi:10.1002/yea.320100008. PMID 8091862.
- ↑ "Distinct 3' UTRs regulate the life-cycle-specific expression of two TCTP paralogs in Trypanosoma brucei". Journal of Cell Science 131 (9): jcs206417. May 2018. doi:10.1242/jcs.206417. PMID 29661850.
- ↑ "The translationally controlled tumor protein TCTP is involved in cell cycle progression and heat stress response in the bloodstream form of Trypanosoma brucei". Microbial Cell 5 (10): 460–468. August 2018. doi:10.15698/mic2018.10.652. PMID 30386790.
- ↑ 11.0 11.1 "Tumor protein Tctp regulates axon development in the embryonic visual system". Development 143 (7): 1134–1148. April 2016. doi:10.1242/dev.131060. PMID 26903505.
- ↑ "Biological effects of Mammalian translationally controlled tumor protein (TCTP) on cell death, proliferation, and tumorigenesis". Biochemistry Research International 2012: 204960. 2012. doi:10.1155/2012/204960. PMID 22675633.
- ↑ "The growth-related, translationally controlled protein P23 has properties of a tubulin binding protein and associates transiently with microtubules during the cell cycle". Journal of Cell Science 112 ( Pt 8) (8): 1257–1271. April 1999. doi:10.1242/jcs.112.8.1257. PMID 10085260. https://hal.archives-ouvertes.fr/hal-02381728/file/JCS%20P23.pdf.
- ↑ "Complex relationship between TCTP, microtubules and actin microfilaments regulates cell shape in normal and cancer cells". Carcinogenesis 30 (4): 555–565. April 2009. doi:10.1093/carcin/bgp022. PMID 19168579.
- ↑ "Reciprocal repression between P53 and TCTP". Nature Medicine 18 (1): 91–99. December 2011. doi:10.1038/nm.2546. PMID 22157679.
- ↑ "Biological models and genes of tumor reversion: cellular reprogramming through tpt1/TCTP and SIAH-1". Proceedings of the National Academy of Sciences of the United States of America 99 (23): 14976–14981. November 2002. doi:10.1073/pnas.222470799. PMID 12399545. Bibcode: 2002PNAS...9914976T.
- ↑ "Translationally controlled tumor protein is a target of tumor reversion". Proceedings of the National Academy of Sciences of the United States of America 101 (43): 15364–15369. October 2004. doi:10.1073/pnas.0406776101. PMID 15489264. Bibcode: 2004PNAS..10115364T.
- ↑ "Molecular identification of an IgE-dependent histamine-releasing factor". Science 269 (5224): 688–690. August 1995. doi:10.1126/science.7542803. PMID 7542803. Bibcode: 1995Sci...269..688M.
- ↑ 19.0 19.1 "TCTP protects from apoptotic cell death by antagonizing bax function". Cell Death and Differentiation 15 (8): 1211–1220. August 2008. doi:10.1038/cdd.2008.18. PMID 18274553.
- ↑ "Stabilization and enhancement of the antiapoptotic activity of mcl-1 by TCTP". Molecular and Cellular Biology 25 (8): 3117–3126. April 2005. doi:10.1128/MCB.25.8.3117-3126.2005. PMID 15798198.
- ↑ "TCTP contains a BH3-like domain, which instead of inhibiting, activates Bcl-xL". Scientific Reports 6: 19725. January 2016. doi:10.1038/srep19725. PMID 26813996. Bibcode: 2016NatSR...619725T.
- ↑ "Structural Insights into TCTP and Its Interactions with Ligands and Proteins". Results and Problems in Cell Differentiation 64: 9–46. 2016. doi:10.1007/978-3-319-67591-6_2. ISBN 978-3-319-67590-9. PMID 29149402. https://hal.archives-ouvertes.fr/hal-02309075/file/chapitre_TCTP_4Hal.pdf.
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