Genomic Organization of Mouse and Human 65 kDa FK506-Binding Protein Genes and Evolution of the FKBP Multigene Family

Patterson, Charles E.; Gao, Jimin; Rooney, Alejandro P.; Davis, Elaine C.

doi:10.1006/geno.2002.6777

Cited by 32 publications

(20 citation statements)

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“…Coss et al described the mFKBP65 protein to be both a glycoprotein and a phosphoprotein (10), and later Patterson et al located the mouse protein to the ER by immunofluorescent microscopy (11). The mFKBP10 and hFKBP10 are very similar: 84% similar on the nucleotide level and 89% at the amino acid level (6), with almost identical sizes except for one additional amino acid in hFKBP65 . To our knowledge, no functional studies have been made on the hFKBP10 or the protein (hFKBP65) encoded by the gene, and neither gene nor protein have been found associated with any form of cancer until now.…”

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confidence: 67%

“…hFKBP10 is a member of the large gene family of immunophilins, comprised of two structurally unrelated subgroups defined by the proteins ability to bind either FK506 (the FK506-binding proteins (FKBPs) 1 ) or cyclosporin A (the cyclophilins). The gene hFKBP10 (human FK506-binding protein number 10) encodes a predicted 65-kDa protein named hFKBP65, containing four peptidyl prolyl cis/trans isomerase domains (PPIase domains), an endoplasmic reticulum (ER) target sequence, and a putative ER retention signal (6,7). The mouse homologue of hFKBP65, mFKBP65, has been associated with two different pathways in mice, either being associated with the chaperone Hsp90 and the serine kinase cRaf-1 in the cytoplasm (8) or, alternatively, being associated with the extracellular matrix protein tropoelastin in the ER (9).…”

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confidence: 99%

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Human FK506 Binding Protein 65 Is Associated with Colorectal Cancer

Olesen

Christensen

Sørensen

et al. 2005

Molecular & Cellular Proteomics

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We initiated the present study to identify new genes associated with colorectal cancer. In a previously published microarray study an EST (W80763), later identified as the gene hFKBP10 (NM_021939), was found to be strongly expressed in tumors while absent in the normal mucosa. Here we describe this gene hFKBP10 together with its encoded protein hFKBP65 as a novel marker associated with colorectal cancer. Analysis of 31 colorectal adenocarcinomas and 14 normal colorectal mucosa by RealTime PCR for hFKBP10 showed a significant up-regulation in tumors, when compared with normal mucosa. Immunohistochemical analysis of 26 adenocarcinomas and matching normal mucosa, as well as benign hyperplastic polyps and adenomas, using a monoclonal antihFKBP65 antibody, showed that the protein was not present in normal colorectal epithelial cells, but strongly expressed in the tumor cells of colorectal cancer. The protein was also expressed in fibroblasts of both normal mucosa and tumor tissue. Western blot analysis of matched tumors and normal mucosa supported the finding of increased hFKBP65 expression in tumors compared with normal mucosa, in addition to identifying the molecular mass of hFKBP65 to ϳ72 kDa. Cellular localization and glycosylation studies revealed the hFKBP65 protein to be localized in the endoplasmic reticulum, and to be N-glycosylated. In conclusion, the protein hFKBP65 is associated with colorectal cancer, and we hypothesize the protein to be involved in fibroblast and transformed epithelial cell-specific protein synthesis in the endoplasmic reticulum. Molecular & Cellular Proteomics 4:534 -544, 2005.Despite progresses made during the last decades, sporadic colorectal cancer remains one of the most frequent neoplasias in the Western world. Approximately 50% of patients diagnosed with colorectal cancer die within 5 years from diagnosis (1); however, an early diagnosis will improve the patients' chance of survival dramatically. Multiple genetic alterations are necessary to develop colorectal cancer (2), but very few colorectal cancers have gone through the exact same series of alterations. Furthermore, recent studies have shown a differential gene expression between the proximal and the distal colon (3, 4), which means that the localization of a tumor within the colon also has to be taken into account when investigating this disease. Altogether, new models based on a deeper molecular understanding of the disease are required to improve screening, diagnosis, treatment, and, ultimately, survival.In a previous study (5), we identified a subset of genes and ESTs up-or down-regulated in the four different stages of colorectal cancer (Dukes stages A, B, C, and D) as compared with normal colorectal mucosa (N). The expression of especially one EST (W80763), later identified as the gene hFKBP10 (NM_021939), seemed to be a potentially good marker for colorectal cancer. The gene was not expressed in normal colorectal mucosa and highly expressed in all four Dukes stages. hFKBP10 is a member of the large gene family of immu...

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confidence: 67%

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confidence: 99%

Human FK506 Binding Protein 65 Is Associated with Colorectal Cancer

Olesen

Christensen

Sørensen

et al. 2005

Molecular & Cellular Proteomics

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“…The FKBd sequence of approximately 110 amino acids ( Fig. 1) adopts a well-conserved tertiary structure [12][13][14], primarily containing six anti-parallel beta sheets connected by a number of solvent-exposed loops, one of which contains a short alpha helix (Fig. 2).…”

Section: The Fk506-binding Domainmentioning

confidence: 99%

The FKBP families of higher plants: Exploring the structures and functions of protein interaction specialists

2012

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a b s t r a c tThe FK506-binding proteins (FKBPs) are known both as the receptors for immunosuppressant drugs and as prolyl isomerase (PPIase) enzymes that catalyse rotation of prolyl bonds. FKBPs are characterised by the inclusion of at least one FK506-binding domain (FKBd), the receptor site for proline and the active site for PPIase catalysis. The FKBPs form large and diverse families in most organisms, with the largest FKBP families occurring in higher plants. Plant FKBPs are molecular chaperones that interact with specific protein partners to regulate a diversity of cellular processes. Recent studies have found that plant FKBPs operate in intricate and coordinated mechanisms for regulating stress response and development processes, and discoveries of new interaction partners expand their cellular influences to gene expression and photosynthetic adaptations. This review presents an examination of the molecular and structural features and functional roles of the higher plant FKBP family within the context of these recent findings, and discusses the significance of domain conservation and variation for the development of a diverse, versatile and complex chaperone family.

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“…The largest group of human FKBPs are the secretory pathway class of FKBPs (Davis, 2000), which comprise FKBP13 (Jin et al, 1991), FKBP19 (this article), FKBP22 (Patterson et al, 2002), two splice variants of FKBP23 (one of which was previously identified in mouse: Nakamura et al, 1998), FKBP60 (Shadidy et al, 1999), and FKBP65 (Patterson et al, 2002). Members of this group are distinguishable from other FKBPs by the presence of N-terminal, leucine-rich, cleavable signal peptides and C-terminal endoplasmic reticulum (ER)-retention motifs, which in most cases is a variant of the canonical KDEL motif (Munro and Pelham, 1987).…”

Section: Resultsmentioning

confidence: 99%

“…The FK506-binding protein (FKBP) family share a high degree of sequence and structural homology and PPIase activity that is specifically inhibited by FK506 or rapamycin (Kay, 1996). Since the discovery of the first FKBP (Siekierka et al, 1989), several members of this family have been characterised in humans and other organisms (Patterson et al, 2002, Galat, 2003. Each member of the FKBP family contains one or more PPIase domain, which shows high sequence homology with the most abundant member, FKBP12.…”

Section: Introductionmentioning

confidence: 99%