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词条 Tpr-met fusion protein
释义

  1. Structure

  2. Experimental evidences

      Effects in muscle    Skeletal muscle    Cardiac muscle  

  3. References

  4. External links

Tpr-Met fusion protein is an oncogene fusion protein consisting of TPR and MET.[1]

Structure

Tpr-Met was generated following a chromosomal rearrangement induced by the treatment of a human osteogenic sarcoma cell line with the carcinogen N-methyl-N'-nitronitrosoguanidine. The genomic rearrangement fuses two genetic loci,translocated promoter region, from chromosome 1q25 which encodes a dimerization leucine zipper motif, and MET, from chromosome 7q31 which contributes the kinase domain and carboxy-terminus of the Met RTK.[2][3] The resulting 65 kDa cytoplasmic Tpr-Met oncoprotein forms a dimer mediated through the Tpr leucine zipper.[4]

The Tpr-Met fusion protein lacks the extracellular, transmembrane and juxtamembrane domains of c-Met receptor, and has gained the Tpr dimerization motif, which allows constitutive and ligand-independent activation of the kinase. The loss of juxtamembrane sequences, necessary for the negative regulation of kinase activity and receptor degradation, prolongs duration of Met signalling.[5]

Experimental evidences

Effects in muscle

Skeletal muscle

Specific expression of Tpr-Met in terminally-differentiated skeletal muscle causes muscle wasting in vivo and exerts anti-differentiation effects in terminally differentiated myotubes.[6][7] Constitutive activation of MET signaling has been suggested to cause defects in myogenic differentiation, contributing to rhabdomyosarcoma development and progression.[8]

Cardiac muscle

In a transgenic model, cardiac-specific expression of Tpr-Met oncogene during postnatal life causes heart failure with early-onset.[9]

References

1. ^{{Cite journal|vauthors=Mak HH, Peschard P, Lin T, Naujokas MA, Zuo D, Park M |title=Oncogenic activation of the Met receptor tyrosine kinase fusion protein, Tpr-Met, involves exclusion from the endocytic degradative pathway |journal= Oncogene|volume= 26|issue= 51|pages= 7213–21|year=2007 |pmid=17533376 |doi=10.1038/sj.onc.1210522}}
2. ^{{Cite journal|title = Characterization of the rearranged tpr-met oncogene breakpoint|journal = Molecular and Cellular Biology|date = 1987-02-01|issn = 0270-7306|pmc = 365151|pmid = 3821733|pages = 921–924|volume = 7|issue = 2|first = M.|last = Dean|first2 = M.|last2 = Park|first3 = G. F.|last3 = Vande Woude|doi=10.1128/mcb.7.2.921}}
3. ^{{Cite journal|title = Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors|journal = Proceedings of the National Academy of Sciences of the United States of America|date = 1987-09-01|issn = 0027-8424|pmc = 299079|pmid = 2819873|pages = 6379–6383|volume = 84|issue = 18|first = M.|last = Park|first2 = M.|last2 = Dean|first3 = K.|last3 = Kaul|first4 = M. J.|last4 = Braun|first5 = M. A.|last5 = Gonda|first6 = G.|last6 = Vande Woude|doi=10.1073/pnas.84.18.6379}}
4. ^{{Cite journal|title = Dimerization mediated through a leucine zipper activates the oncogenic potential of the met receptor tyrosine kinase|journal = Molecular and Cellular Biology|date = 1993-11-01|issn = 0270-7306|pmc = 364734|pmid = 8413267|pages = 6711–6722|volume = 13|issue = 11|first = G. A.|last = Rodrigues|first2 = M.|last2 = Park|doi=10.1128/mcb.13.11.6711}}
5. ^{{Cite journal|title = From Tpr-Met to Met, tumorigenesis and tubes|journal = Oncogene|date = 2007-02-26|issn = 0950-9232|pmid = 17322912|pages = 1276–1285|volume = 26|issue = 9|doi = 10.1038/sj.onc.1210201|first = P.|last = Peschard|first2 = M.|last2 = Park}}
6. ^{{Cite journal|title = Conditional activation of MET in differentiated skeletal muscle induces atrophy|journal = The Journal of Biological Chemistry|date = 2007-03-02|issn = 0021-9258|pmid = 17194700|pages = 6812–6822|volume = 282|issue = 9|doi = 10.1074/jbc.M610916200|first = Tiziana|last = Crepaldi|first2 = Francesca|last2 = Bersani|first3 = Claudio|last3 = Scuoppo|first4 = Paolo|last4 = Accornero|first5 = Chiara|last5 = Prunotto|first6 = Riccardo|last6 = Taulli|first7 = Paolo E.|last7 = Forni|first8 = Christian|last8 = Leo|first9 = Roberto|last9 = Chiarle}}
7. ^{{Cite journal|title = Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes|url = http://www.mdpi.com/2227-9059/3/1/124|journal = Biomedicines|date = 2015-02-12|pages = 124–137|volume = 3|issue = 1|doi = 10.3390/biomedicines3010124|first = Valentina|last = Sala|first2 = Simona|last2 = Gallo|first3 = Stefano|last3 = Gatti|first4 = Elisa|last4 = Vigna|first5 = Antonio|last5 = Ponzetto|first6 = Tiziana|last6 = Crepaldi}}
8. ^{{Cite journal|title = Constitutive activation of MET signaling impairs myogenic differentiation of rhabdomyosarcoma and promotes its development and progression|journal = Oncotarget|date = 2015-09-08|issn = 1949-2553|pmid = 26384300|first = Klaudia|last = Skrzypek|first2 = Anna|last2 = Kusienicka|first3 = Barbara|last3 = Szewczyk|first4 = Tomasz|last4 = Adamus|first5 = Ewa|last5 = Lukasiewicz|first6 = Katarzyna|last6 = Miekus|first7 = Marcin|last7 = Majka|doi=10.18632/oncotarget.5145|volume=6|pages=31378–98|pmc=4741613}}
9. ^{{Cite journal|title = Activated Met Signalling in the Developing Mouse Heart Leads to Cardiac Disease|journal = PLoS ONE|date = 2011-02-09|issn = 1932-6203|pmc = 3036588|pmid = 21347410|volume = 6|issue = 2|doi = 10.1371/journal.pone.0014675|first = Christian|last = Leo|first2 = Valentina|last2 = Sala|first3 = Mara|last3 = Morello|first4 = Amedeo|last4 = Chiribiri|first5 = Ilan|last5 = Riess|first6 = Daniele|last6 = Mancardi|first7 = Stefano|last7 = Schiaffino|first8 = Carola|last8 = Ponzetto|first9 = Tiziana|last9 = Crepaldi|pages=e14675}}

External links

  • {{MeshName|Fusion+Proteins,+tpr-met}}
{{Biochem-stub}}

1 : Engineered proteins
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