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FKBP family proteins: immunophilins with versatile biological functions.
Neurosignals. 2008; 16(4):318-25.N

Abstract

Immunophilins consist of a family of highly conserved proteins binding with immunosuppressive drugs such as FK506, rapamycin and cyclosporin A. FK506-binding protein (FKBP) is one of two major immunophilins and most of FKBP family members bind FK506 and show peptidylprolyl cis/trans isomerase (PPIase) activity. Small size FKBP family members contain only FK506-binding domain, while FKBPs with large molecular weights possess extra domains such as tetratricopeptide repeat domains, calmodulin binding and transmembrane motifs. FKBPs are involved in several biochemical processes including protein folding, receptor signaling, protein trafficking and transcription. FKBP family proteins play important functional roles in the T-cell activation, when complexed with their ligands. The roles of immunophilins in protein transportation and apoptosis through their molecular interactions with receptors or proteins have emerged recently. Moreover, therapeutic implications of immunophilin ligands in treating neurodegenerative disorders have been accumulating. FK506 and its derivatives with no immunosuppressive activities bind to the conserved active sites of the canonical FKBP members such as FKBP12, which shows PPIase activity. These immunophilin ligands show variable efficacy in animal models for Parkinson's disease, dementia, and spinal cord injury, where the canonical immunophilins function as chaperones and are associate with the protein folding and modulation of oxidative stress. On the other hand, in the noncanonical FKBP members such as FKBP38, FK506-binding site is not conserved and shows neither PPIase activity nor affinity to FK506. Interestingly, the small molecule-mediated inhibition of the noncanonical member of FKBP family appears to cause neuronal protection and induce proliferation of neuronal stem cells in a rat focal cerebral ischemia model. Currently, the mechanisms of actions remain unclear. This review focuses on molecular characteristics of the canonical and noncanonical FKBP family members and the biological functions of their ligands in performing neuroprotective and neurotrophic activities.

Authors+Show Affiliations

School of Biological Science, Nanyang Technological University, Singapore, Singapore.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

18635947

Citation

Kang, Cong Bao, et al. "FKBP Family Proteins: Immunophilins With Versatile Biological Functions." Neuro-Signals, vol. 16, no. 4, 2008, pp. 318-25.
Kang CB, Hong Y, Dhe-Paganon S, et al. FKBP family proteins: immunophilins with versatile biological functions. Neurosignals. 2008;16(4):318-25.
Kang, C. B., Hong, Y., Dhe-Paganon, S., & Yoon, H. S. (2008). FKBP family proteins: immunophilins with versatile biological functions. Neuro-Signals, 16(4), 318-25. https://doi.org/10.1159/000123041
Kang CB, et al. FKBP Family Proteins: Immunophilins With Versatile Biological Functions. Neurosignals. 2008;16(4):318-25. PubMed PMID: 18635947.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FKBP family proteins: immunophilins with versatile biological functions. AU - Kang,Cong Bao, AU - Hong,Ye, AU - Dhe-Paganon,Sirano, AU - Yoon,Ho Sup, Y1 - 2008/07/18/ PY - 2008/7/19/pubmed PY - 2009/2/5/medline PY - 2008/7/19/entrez SP - 318 EP - 25 JF - Neuro-Signals JO - Neurosignals VL - 16 IS - 4 N2 - Immunophilins consist of a family of highly conserved proteins binding with immunosuppressive drugs such as FK506, rapamycin and cyclosporin A. FK506-binding protein (FKBP) is one of two major immunophilins and most of FKBP family members bind FK506 and show peptidylprolyl cis/trans isomerase (PPIase) activity. Small size FKBP family members contain only FK506-binding domain, while FKBPs with large molecular weights possess extra domains such as tetratricopeptide repeat domains, calmodulin binding and transmembrane motifs. FKBPs are involved in several biochemical processes including protein folding, receptor signaling, protein trafficking and transcription. FKBP family proteins play important functional roles in the T-cell activation, when complexed with their ligands. The roles of immunophilins in protein transportation and apoptosis through their molecular interactions with receptors or proteins have emerged recently. Moreover, therapeutic implications of immunophilin ligands in treating neurodegenerative disorders have been accumulating. FK506 and its derivatives with no immunosuppressive activities bind to the conserved active sites of the canonical FKBP members such as FKBP12, which shows PPIase activity. These immunophilin ligands show variable efficacy in animal models for Parkinson's disease, dementia, and spinal cord injury, where the canonical immunophilins function as chaperones and are associate with the protein folding and modulation of oxidative stress. On the other hand, in the noncanonical FKBP members such as FKBP38, FK506-binding site is not conserved and shows neither PPIase activity nor affinity to FK506. Interestingly, the small molecule-mediated inhibition of the noncanonical member of FKBP family appears to cause neuronal protection and induce proliferation of neuronal stem cells in a rat focal cerebral ischemia model. Currently, the mechanisms of actions remain unclear. This review focuses on molecular characteristics of the canonical and noncanonical FKBP family members and the biological functions of their ligands in performing neuroprotective and neurotrophic activities. SN - 1424-8638 UR - https://www.unboundmedicine.com/medline/citation/18635947/FKBP_family_proteins:_immunophilins_with_versatile_biological_functions_ L2 - https://www.karger.com?DOI=10.1159/000123041 DB - PRIME DP - Unbound Medicine ER -