Disease relevance of FAF1

• Clinical study has revealed that FAF1 is significantly reduced in gastric carcinomas [1].
• Here, we report the full length human FAF1 cDNA sequence, expression of FAF1 in Escherichia coli and purification and characterization of FAF1 as a substrate for CK2 [2].
• Additionally, 31 colorectal carcinomas were analyzed for expression of FAF1 [3].
• Also, the reduction of FAF1 is likely to be specific for gastric cancer, which might be due to the fact that signet ring cells are most frequently found in gastric cancers [3].
• The aggression profile of patients with Duodenal Peptic Ulcer (DPU) (n = 39) was assessed by means of five self-rating scales (FAF 1, FAF 3, PDS-Extp, PDS-Intp, PDS-Dom) and was compared with a matched normal control group (n = 39) and a psychiatric outpatient sample (n = 67) [4].

High impact information on FAF1

• These results suggest that hFAF1 binding to ubiquitinated protein and VCP is involved in the ubiquitin-proteasome pathway [5].
• The overexpression of hFAF1 and a truncated UBA domain inhibited the degradation of ubiquitinated proteins and increased cell death [5].
• These results suggest that hFAF1 prevents cells from recovery after stress by binding to and inhibiting the chaperone activity of Hsp70 [6].
• Interaction mapping indicated that the 82-180 sequence of hFAF1 directly binds to the N-terminal region containing sequence 1-120 of Hsc70/Hsp70 [6].
• NF-kappaB activation induced by tumor necrosis factor (TNF)-alpha, interleukin-1beta, and lipopolysaccharide was also inhibited by FAF1 overexpression [7].

Biological context of FAF1

• Cell death by overexpression of FAF1 was suppressed significantly in both FADD- and caspase-8-deficient Jurkat cells when compared with that in their parental Jurkat cells [8].
• In addition, the FAF1 deletion mutant lacking the N terminus where Fas, FADD, and caspase-8 interact protected Jurkat cells from Fas-induced apoptosis demonstrating dominant-negative phenotype [8].
• Based on the fact that FAF1 is a Fas-binding protein, we asked if FAF1 interacted with other members of the Fas-death-inducing signaling complex (Fas-DISC) such as Fas-associated death domain protein (FADD) and caspase-8 [8].
• Introduction of antisense FAF1 construct inhibited DEF assembly and chemotherapeutic-induced apoptosis [1].
• Furthermore, we analyzed putative physiological functions of FAF1 phosphorylation [9].

Anatomical context of FAF1

• Overexpression of FAF1 in Jurkat cells caused significant apoptotic death [8].
• By confocal microscopic analysis, both Fas and FAF1 were detected in the cytoplasmic membrane before Fas activation, and in the cytoplasm after Fas activation [8].
• Not much is known about the function of FAF1, but it has been found that it is able to potentiate Fas-induced apoptosis in cell lines [3].
• Here, FAF1 was only reduced in 16% of the carcinomas when compared to non-neoplastic colorectal mucosa [3].
• We found that FAF1 was reduced in 50% (29/58) of the gastric carcinomas analyzed as compared to non-neoplastic gastric mucosa from the same patients [3].

Associations of FAF1 with chemical compounds

• Overexpression of FAF1 enhanced DEF assembly and cell death induced by chemotherapeutics such as staurosporine (STS), cisplatin (CDDP) and etoposide (VP16) [1].
• Furthermore, silencing FAF1 by RNA interference augments capsaicin-sensitive current in native sensory neurons [10].
• Using CK2beta as a bait in a two-hybrid library screening several new putative cellular partners have been identified, among them the S6 kinase p90rsk, the putative tumor suppressor protein Doc-1, the Fas-associated protein FAF1, the mitochondrial translational initiation factor 2 and propionyl CoA carboxylase beta subunit [11].

Physical interactions of FAF1

• FAF1 could interact with caspase-8 and FADD in vivo as well as in vitro [8].

Co-localisations of FAF1

• FADD and caspase-8 colocalized with Fas in Jurkat cells validating the presence of FAF1 in the authentic Fas-DISC [8].

Other interactions of FAF1

• In the coimmunoprecipitation with an anti-Fas antibody (APO-1) in Jurkat cells, endogenous FAF1 was associated with the precipitates in which caspase-8 was present [8].
• Human Fas-associated factor 1, interacting with ubiquitinated proteins and valosin-containing protein, is involved in the ubiquitin-proteasome pathway [5].
• By employing co-immunoprecipitation and peptide mass fingerprinting using matrix-assisted laser desorption ionization time-of-flight mass spectrometry, we found that hFAF1 binds to the 70-kDa heat shock protein family (Hsc70/Hsp70) [6].
• Here, we identify Fas-associated factor 1 (FAF1) as a regulatory factor, which is coexpressed with and binds to TRPV1 in sensory neurons [10].
• The N-terminal region (amino acid 1 approximately 201) including the upstream ubiquitin homology domain of hFAF1 could bind with the death domain of Fas unlike that of qFAF1 whose binding region with Fas could not be determined [12].

Analytical, diagnostic and therapeutic context of FAF1

• Confocal microscopy revealed that FAF1 was present in DEFs together with FADD and caspase-8 [1].
• Thus, 58 human gastric carcinomas were collected, and the expression of FAF1 was analyzed by Western blotting and in a few cases also by immunohistochemistry [3].
• Here, we used yeast two-hybrid assays to identify Fas-associated factor 1 (FAF1) as a protein interacting with the pyrin domains of several PYPAFs [13].

References