Role of T198 modification in the regulation of p27(Kip1) protein stability and function.

The tumor suppressor gene p27(Kip1) plays a fundamental role in human cancer progression. Its expression and/or functions are altered in almost all the different tumor histotype analyzed so far. Recently, it has been demonstrated that the tumor suppression function of p27 resides not only in the abi...

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Autores principales:	Monica Schiappacassi, Sara Lovisa, Francesca Lovat, Linda Fabris, Alfonso Colombatti, Barbara Belletti, Gustavo Baldassarre
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/72b72133c88743a2b53bdf151ff6ae33
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spelling	oai:doaj.org-article:72b72133c88743a2b53bdf151ff6ae332021-11-18T06:57:20ZRole of T198 modification in the regulation of p27(Kip1) protein stability and function.1932-620310.1371/journal.pone.0017673https://doaj.org/article/72b72133c88743a2b53bdf151ff6ae332011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21423803/?tool=EBIhttps://doaj.org/toc/1932-6203The tumor suppressor gene p27(Kip1) plays a fundamental role in human cancer progression. Its expression and/or functions are altered in almost all the different tumor histotype analyzed so far. Recently, it has been demonstrated that the tumor suppression function of p27 resides not only in the ability to inhibit Cyclins/CDKs complexes through its N-terminal domain but also in the capacity to modulate cell motility through its C-terminal portion. Particular interest has been raised by the last amino-acid, (Threonine 198) in the regulation of both protein stability and cell motility.Here, we describe that the presence of Threonine in position 198 is of primary importance for the regulation of the protein stability and for the control of cell motility. However, while the control of cell motility is dependent on the phosphorylation of T198, the stability of the protein is specifically controlled by the steric hindrance of the last amino acid. The effects of T198 modification on protein stability are not linked to the capacity of p27 to bind Cyclins/CDKs complexes and/or the F-box protein Skp2. Conversely, our results support the hypothesis that conformational changes in the disordered structure of the C-terminal portion of p27 are important in its ability to be degraded via a proteasome-dependent mechanism. On the other hand T198 phosphorylation favors p27/stathmin interaction eventually contributing to the regulation of cell motility, supporting the hypothesis that the presence of T198 is fundamental for the regulation of p27 functions.Monica SchiappacassiSara LovisaFrancesca LovatLinda FabrisAlfonso ColombattiBarbara BellettiGustavo BaldassarrePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e17673 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Monica Schiappacassi Sara Lovisa Francesca Lovat Linda Fabris Alfonso Colombatti Barbara Belletti Gustavo Baldassarre Role of T198 modification in the regulation of p27(Kip1) protein stability and function.
description	The tumor suppressor gene p27(Kip1) plays a fundamental role in human cancer progression. Its expression and/or functions are altered in almost all the different tumor histotype analyzed so far. Recently, it has been demonstrated that the tumor suppression function of p27 resides not only in the ability to inhibit Cyclins/CDKs complexes through its N-terminal domain but also in the capacity to modulate cell motility through its C-terminal portion. Particular interest has been raised by the last amino-acid, (Threonine 198) in the regulation of both protein stability and cell motility.Here, we describe that the presence of Threonine in position 198 is of primary importance for the regulation of the protein stability and for the control of cell motility. However, while the control of cell motility is dependent on the phosphorylation of T198, the stability of the protein is specifically controlled by the steric hindrance of the last amino acid. The effects of T198 modification on protein stability are not linked to the capacity of p27 to bind Cyclins/CDKs complexes and/or the F-box protein Skp2. Conversely, our results support the hypothesis that conformational changes in the disordered structure of the C-terminal portion of p27 are important in its ability to be degraded via a proteasome-dependent mechanism. On the other hand T198 phosphorylation favors p27/stathmin interaction eventually contributing to the regulation of cell motility, supporting the hypothesis that the presence of T198 is fundamental for the regulation of p27 functions.
format	article
author	Monica Schiappacassi Sara Lovisa Francesca Lovat Linda Fabris Alfonso Colombatti Barbara Belletti Gustavo Baldassarre
author_facet	Monica Schiappacassi Sara Lovisa Francesca Lovat Linda Fabris Alfonso Colombatti Barbara Belletti Gustavo Baldassarre
author_sort	Monica Schiappacassi
title	Role of T198 modification in the regulation of p27(Kip1) protein stability and function.
title_short	Role of T198 modification in the regulation of p27(Kip1) protein stability and function.
title_full	Role of T198 modification in the regulation of p27(Kip1) protein stability and function.
title_fullStr	Role of T198 modification in the regulation of p27(Kip1) protein stability and function.
title_full_unstemmed	Role of T198 modification in the regulation of p27(Kip1) protein stability and function.
title_sort	role of t198 modification in the regulation of p27(kip1) protein stability and function.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/72b72133c88743a2b53bdf151ff6ae33
work_keys_str_mv	AT monicaschiappacassi roleoft198modificationintheregulationofp27kip1proteinstabilityandfunction AT saralovisa roleoft198modificationintheregulationofp27kip1proteinstabilityandfunction AT francescalovat roleoft198modificationintheregulationofp27kip1proteinstabilityandfunction AT lindafabris roleoft198modificationintheregulationofp27kip1proteinstabilityandfunction AT alfonsocolombatti roleoft198modificationintheregulationofp27kip1proteinstabilityandfunction AT barbarabelletti roleoft198modificationintheregulationofp27kip1proteinstabilityandfunction AT gustavobaldassarre roleoft198modificationintheregulationofp27kip1proteinstabilityandfunction
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Role of T198 modification in the regulation of p27(Kip1) protein stability and function.

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