Cargando…

The Emerging Role of Large Immunophilin FK506 Binding Protein 51 in Cancer

FK506 binding protein 51 (FKBP51) is an immunophilin physiologically expressed in lymphocytes. Very recently, aberrant expression of this protein was found in melanoma; FKBP51 expression correlates with melanoma aggressiveness and is maximal in metastatic lesions. FKBP51 promotes NF-κB activation an...

Descripción completa

Detalles Bibliográficos
Autores principales: Romano, S, Sorrentino, A, Di Pace, AL, Nappo, G, Mercogliano, C, Romano, MF
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613799/
https://www.ncbi.nlm.nih.gov/pubmed/22087835
http://dx.doi.org/10.2174/092986711798194333
_version_ 1782264781699284992
author Romano, S
Sorrentino, A
Di Pace, AL
Nappo, G
Mercogliano, C
Romano, MF
author_facet Romano, S
Sorrentino, A
Di Pace, AL
Nappo, G
Mercogliano, C
Romano, MF
author_sort Romano, S
collection PubMed
description FK506 binding protein 51 (FKBP51) is an immunophilin physiologically expressed in lymphocytes. Very recently, aberrant expression of this protein was found in melanoma; FKBP51 expression correlates with melanoma aggressiveness and is maximal in metastatic lesions. FKBP51 promotes NF-κB activation and is involved in the resistance to genotoxic agents, including anthracyclines and ionizing radiation. FKBP51 is a cochaperone with peptidyl-prolyl isomerase activity that regulates several biological processes through protein-protein interaction. There is increasing evidence that FKBP51 hyperexpression is associated with cancer and this protein has a relevant role in sustaining cell growth, malignancy, and resistance to therapy. There is also evidence that FKBP ligands are potent anticancer agents, in addition to their immunosuppressant activity. In particular, rapamycin and its analogs have shown antitumor activity across a variety of human cancers in clinical trials. Although, classically, rapamycin actions are ascribed to inhibition of mTOR, recent studies indicate FKBP51 is also an important molecular determinant of the drug’s anticancer activity. The aim of this article is to review the functions of FKBP51, especially in view of the recent findings that this protein is a potential oncogene when deregulated and a candidate target for signaling therapies against cancer.
format Online
Article
Text
id pubmed-3613799
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Bentham Science Publishers
record_format MEDLINE/PubMed
spelling pubmed-36137992013-04-04 The Emerging Role of Large Immunophilin FK506 Binding Protein 51 in Cancer Romano, S Sorrentino, A Di Pace, AL Nappo, G Mercogliano, C Romano, MF Curr Med Chem Article FK506 binding protein 51 (FKBP51) is an immunophilin physiologically expressed in lymphocytes. Very recently, aberrant expression of this protein was found in melanoma; FKBP51 expression correlates with melanoma aggressiveness and is maximal in metastatic lesions. FKBP51 promotes NF-κB activation and is involved in the resistance to genotoxic agents, including anthracyclines and ionizing radiation. FKBP51 is a cochaperone with peptidyl-prolyl isomerase activity that regulates several biological processes through protein-protein interaction. There is increasing evidence that FKBP51 hyperexpression is associated with cancer and this protein has a relevant role in sustaining cell growth, malignancy, and resistance to therapy. There is also evidence that FKBP ligands are potent anticancer agents, in addition to their immunosuppressant activity. In particular, rapamycin and its analogs have shown antitumor activity across a variety of human cancers in clinical trials. Although, classically, rapamycin actions are ascribed to inhibition of mTOR, recent studies indicate FKBP51 is also an important molecular determinant of the drug’s anticancer activity. The aim of this article is to review the functions of FKBP51, especially in view of the recent findings that this protein is a potential oncogene when deregulated and a candidate target for signaling therapies against cancer. Bentham Science Publishers 2011-12 2011-12 /pmc/articles/PMC3613799/ /pubmed/22087835 http://dx.doi.org/10.2174/092986711798194333 Text en © 2011 Bentham Science Publishers http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Romano, S
Sorrentino, A
Di Pace, AL
Nappo, G
Mercogliano, C
Romano, MF
The Emerging Role of Large Immunophilin FK506 Binding Protein 51 in Cancer
title The Emerging Role of Large Immunophilin FK506 Binding Protein 51 in Cancer
title_full The Emerging Role of Large Immunophilin FK506 Binding Protein 51 in Cancer
title_fullStr The Emerging Role of Large Immunophilin FK506 Binding Protein 51 in Cancer
title_full_unstemmed The Emerging Role of Large Immunophilin FK506 Binding Protein 51 in Cancer
title_short The Emerging Role of Large Immunophilin FK506 Binding Protein 51 in Cancer
title_sort emerging role of large immunophilin fk506 binding protein 51 in cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613799/
https://www.ncbi.nlm.nih.gov/pubmed/22087835
http://dx.doi.org/10.2174/092986711798194333
work_keys_str_mv AT romanos theemergingroleoflargeimmunophilinfk506bindingprotein51incancer
AT sorrentinoa theemergingroleoflargeimmunophilinfk506bindingprotein51incancer
AT dipaceal theemergingroleoflargeimmunophilinfk506bindingprotein51incancer
AT nappog theemergingroleoflargeimmunophilinfk506bindingprotein51incancer
AT mercoglianoc theemergingroleoflargeimmunophilinfk506bindingprotein51incancer
AT romanomf theemergingroleoflargeimmunophilinfk506bindingprotein51incancer
AT romanos emergingroleoflargeimmunophilinfk506bindingprotein51incancer
AT sorrentinoa emergingroleoflargeimmunophilinfk506bindingprotein51incancer
AT dipaceal emergingroleoflargeimmunophilinfk506bindingprotein51incancer
AT nappog emergingroleoflargeimmunophilinfk506bindingprotein51incancer
AT mercoglianoc emergingroleoflargeimmunophilinfk506bindingprotein51incancer
AT romanomf emergingroleoflargeimmunophilinfk506bindingprotein51incancer