| Title |
Comparative analysis of FKBP family protein: evaluation, structure, and function in mammals and Drosophila melanogaster
|
|---|---|
| Published in |
BMC Developmental Biology, March 2018
|
| DOI | 10.1186/s12861-018-0167-3 |
| Pubmed ID | |
| Authors |
George Ghartey-Kwansah, Zhongguang Li, Rui Feng, Liyang Wang, Xin Zhou, Frederic Z. Chen, Meng Meng Xu, Odell Jones, Yulian Mu, Shawn Chen, Joseph Bryant, Williams B. Isaacs, Jianjie Ma, Xuehong Xu |
| Abstract |
FK506-binding proteins (FKBPs) have become the subject of considerable interest in several fields, leading to the identification of several cellular and molecular pathways in which FKBPs impact prenatal development and pathogenesis of many human diseases. This analysis revealed differences between how mammalian and Drosophila FKBPs mechanisms function in relation to the immunosuppressant drugs, FK506 and rapamycin. Differences that could be used to design insect-specific pesticides. (1) Molecular phylogenetic analysis of FKBP family proteins revealed that the eight known Drosophila FKBPs share homology with the human FKBP12. This indicates a close evolutionary relationship, and possible origination from a common ancestor. (2) The known FKBPs contain FK domains, that is, a prolyl cis/trans isomerase (PPIase) domain that mediates immune suppression through inhibition of calcineurin. The dFKBP59, CG4735/Shutdown, CG1847, and CG5482 have a Tetratricopeptide receptor domain at the C-terminus, which regulates transcription and protein transportation. (3) FKBP51 and FKBP52 (dFKBP59), along with Cyclophilin 40 and protein phosphatase 5, function as Hsp90 immunophilin co-chaperones within steroid receptor-Hsp90 heterocomplexes. These immunophilins are potential drug targets in pathways associated with normal physiology and may be used to treat a variety of steroid-based diseases by targeting exocytic/endocytic cycling and vesicular trafficking. (4) By associating with presinilin, a critical component of the Notch signaling pathway, FKBP14 is a downstream effector of Notch activation at the membrane. Meanwhile, Shutdown associates with transposons in the PIWI-interacting RNA pathway, playing a crucial role in both germ cells and ovarian somas. Mutations in or silencing of dFKBPs lead to early embryonic lethality in Drosophila. Therefore, further understanding the mechanisms of FK506 and rapamycin binding to immunophilin FKBPs in endocrine, cardiovascular, and neurological function in both mammals and Drosophila would provide prospects in generating unique, insect specific therapeutics targeting the above cellular signaling pathways. This review will evaluate the functional roles of FKBP family proteins, and systematically summarize the similarities and differences between FKBP proteins in Drosophila and Mammals. Specific therapeutics targeting cellular signaling pathways will also be discussed. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | 33% |
| United Kingdom | 1 | 33% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Scientists | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 108 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 108 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 18 | 17% |
| Student > Master | 17 | 16% |
| Researcher | 14 | 13% |
| Student > Bachelor | 10 | 9% |
| Student > Doctoral Student | 4 | 4% |
| Other | 16 | 15% |
| Unknown | 29 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 30 | 28% |
| Agricultural and Biological Sciences | 12 | 11% |
| Medicine and Dentistry | 9 | 8% |
| Neuroscience | 5 | 5% |
| Nursing and Health Professions | 3 | 3% |
| Other | 20 | 19% |
| Unknown | 29 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 February 2021.
All research outputs
#13,373,196
of 23,577,654 outputs
Outputs from BMC Developmental Biology
#198
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Outputs of similar age
#161,754
of 331,359 outputs
Outputs of similar age from BMC Developmental Biology
#2
of 8 outputs
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