Disease relevance of CHAF1A

• BACKGROUND AND PURPOSE: The Caf1 secretion pathway of Yersinia pestis is one of the most well-characterized export machineries [1].
• CONCLUSION: These results suggested that the recombinant hEGF was successfully secreted through the inner membrane of cells into the periplasm and then through the outer membrane into the medium via the action of the signal peptide of Y. pestis Caf1 in E. coli [1].
• Randomised trial comparing two combination chemotherapy regimens (Hexa-CAF vs CHAP-5) in advanced ovarian carcinoma [2].
• The results of this study suggest that CD8+ cells, as well as CAF, arrest HIV replication at the level of viral transcription [3].
• CAF in metastatic breast cancer: standard therapy or another effective regimen [4]?

High impact information on CHAF1A

• Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin [5].
• Herein, we demonstrate that after DNA replication, replicated, but not unreplicated, DNA is also competent for CAF-1-dependent chromatin assembly [5].
• We suggest that PCNA and CAF-1 connect DNA replication to chromatin assembly and the inheritance of epigenetic chromosome states [5].
• However, its normal cellular homolog, c-abl P150, is not detectably phosphorylated on tyrosine in vivo or in vitro [6].
• Just before mitosis, CAF-1 p150 and some HP1 progressively dissociate from heterochromatin concomitant with histone H3 phosphorylation [7].

Chemical compound and disease context of CHAF1A

• 186 patients with advanced epithelial ovarian carcinoma were treated with either a combination of hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil (Hexa-CAF) or cyclophosphamide and hexamethylmelamine alternating with doxorubicin and a 5-day course of cisplatin (CHAP-5) [2].
• PURPOSE: To determine whether biochemical modulation with LV (leucovorin) enhances the efficacy of CAF (cyclophosphamide, doxorubicin, and fluorouracil) against metastatic breast cancer [8].
• PATIENTS AND METHODS: Cancer and Leukemia Group B (CALGB) study 8541, a randomized study of schedule and dose of adjuvant cyclophosphamide, doxorubicin, and fluorouracil (CAF) for stage II breast cancer patients with positive regional lymph nodes, provided data on 1,435 women for analysis [9].
• CONCLUSION: Assessment of angiogenesis does not provide useful information regarding prognosis in node-positive breast cancer patients treated with adjuvant CAF, nor do these measures predict which patients will benefit from dose intensification or addition of tamoxifen [10].
• CONCLUSION: High-dose consolidation with CPA/cDDP/BCNU and ABMS after standard-dose CAF results in a decreased frequency of relapse in patients with high-risk primary breast cancer compared with historical series at the median follow-up of 2.5 years [11].

Biological context of CHAF1A

• We discuss the importance of the PCNA-CAF-1 interaction in the context of DNA damage processing and checkpoint control [12].
• CAF-1 and PCNA are recruited to damaged chromatin undergoing DNA repair of single- and double-strand DNA breaks by the base excision repair and nonhomologous end-joining pathways, respectively, in the absence of extensive DNA synthesis [13].
• Depletion of CAF-1 by RNA interference in bleocin-treated quiescent cells in vivo results in a significant loss of cell viability and an accumulation of DSBs [13].
• We discuss the advantages of using CAF-1 to assess cell proliferation [14].
• Site-directed mutagenesis of this surface blocked CRS2-CAF complex formation, indicating that it is the CAF binding site [15].

Anatomical context of CHAF1A

• We show, using both immunofluorescence and Western blot analysis, that the expression of both CAF-1 large subunits, p150 and p60, is massively down-regulated during quiescence in several cell lines [14].
• Plasma samples from patients with medullary thyroid carcinoma were gel filtered on columns of Bio-Gel P-150, and the immunoreactivity in column effuent fractions was measured with both assays [16].
• This antiviral response, mediated by a novel CD8+ T-cell antiviral factor (CAF), occurs soon after infection and is maintained in asymptomatic individuals [17].
• HL60 cells exhibiting a 140-fold increase in resistance to vincristine contain three surface membrane proteins with molecular weights of 210,000 (P210), 180,000 (P180), and 150,000 (P150) which are highly phosphorylated in vivo and in an in vitro system in the presence of Mn2+ and [gamma-32P]ATP [18].
• CONCLUSION: RhuGM-CSF administered once daily at the 250-micrograms/m2/d level is well tolerated and effective in shortening the duration of the neutrophil nadir by 2 or more days after CAF therapy [19].

Associations of CHAF1A with chemical compounds

• CAF-1 prepared from repair-proficient quiescent cells after induction by bleocin mediates nucleosome assembly in vitro [13].
• Strains bearing deletions in either CCR4 or CAF1/POP2, which encode components of the cytoplasmic mRNA deadenylase complex, were particularly sensitive to HU [20].
• In attempts to identify CAF, we discovered that certain protease inhibitors, particularly leupeptin, can block, by up to 95%, the anti-HIV activity in CD8+ cell culture fluids as well as inhibit CNAR [21].
• Inactivation of either cyclic AMP response element binding protein (CREB)-binding protein (CBP), members of the p160 family of coactivators, or the CBP-associated factor (p/CAF) by nuclear antibody microinjection prevents NF-kappaB-dependent transactivation [22].
• However, the utility of this assay in node-positive patients treated with adjuvant cyclophosphamide, doxorubicin, and fluorouracil (CAF) has not been well studied [10].

Other interactions of CHAF1A

• As aberrant expression of the four proteins was not found in brains of patients with AD, decreased CAF and C21orf2 can be considered specific for DS [23].
• Regulation of PCNA and CAF-1 expression by the two tuberous sclerosis gene products [24].
• Fractionation of the crude venom on DEAE-Sepharose, followed by gel filtration on Bio-Gel P-150 and chromatography on CM-Sepharose, yielded an alpha-proteinase preparation which showed a single band on disc and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and had an activity on casein approximately twice that previously reported [25].
• Arginase was purified from Vigna catjang cotyledons and buffalo liver by chromatographic separations using Bio-Gel P-150, DEAE-cellulose and arginine AH Sepharose 4B affinity columns [26].

Analytical, diagnostic and therapeutic context of CHAF1A

• Regulation of CAF-1 expression is partly controlled at the RNA level, as shown by quantitative reverse transcription-PCR and Northern blot experiments [14].
• To identify the structural differences between CRS2 and bacterial PTHs responsible for CRS2's gains of CAF binding and intron splicing functions, we determined the structure of CRS2 by X-ray crystallography [15].
• This CD8+ cell noncytotoxic antiviral response (CNAR), observed by coculture of CD8+ cells with infected CD4+ cells, is associated with secretion of a CD8+ cell antiviral factor (CAF) [21].
• Only 13% of the CAF patients had a complete response during the first six months of chemotherapy, and this was not significantly different from the complete response rate on CMFP [27].
• The primary end points were time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) for CAF-Z versus CAF, and CAF-ZT versus CAF-Z [28].

References