Fanconi anemia (FA)-associated proteins FANCF and FANCD2 are important components of the FA pathway of DNA crosslink repair. FANCF and FANCD2 have been found to be involved in drug-resistant multiple myeloma, ovarian cancer, non-small-cell lung cancer, and head and neck
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چکیده
The Fanconi anemia (FA)-associated proteins FANCF and FANCD2 are important components of the FA pathway of DNA crosslink repair. FANCF and FANCD2 have been found to be involved in drug-resistant multiple myeloma, ovarian cancer, non-small-cell lung cancer, and head and neck cancer. However, it is unclear whether these two genes participate in adriamycin (ADR)-resistant leukemia. Therefore, the aim of the current study was to investigate FANCF and FANCD2 expression in drug-resistant and drug-sensitive leukemia cells. Western blot analysis revealed enhanced FANCF expression and monoubiquitination of FANCD2 in ADR-resistant cells. Additionally, it was observed that drug-resistant cells had reduced DNA damage compared with drug-sensitive cells. The results of this study indicate that the FA pathway may confer leukemia resistance to ADR via enhanced DNA interstrand crosslink repair.
منابع مشابه
FANCD 2 ( Fanconi anemia , complementation group D 2 )
The FA complex is comprised of: FANCA, FANCC, FANCE, FANCF, and FANCG; this complex is only found in the nucleus. FANCA and FANCG form a complex in the cytoplasm, through a N-term FANCA (involving the nuclear localization signal) FANCG interaction; FANCC join the complex; phosphorylation of FANCA would induce its translocation into the nucleus.This FA complex translocates into the nucleus, wher...
متن کاملFANCA ( Fanconi anaemia complementation group A )
Part of the FA complex with FANCC, FANCE, FANCF, and FANCG; this complex is only found in the nucleus. FANCA and FANCG form a complex in the cytoplasm, through a N-term FANCA (involving the nuclear localization signal) FANCG interaction; FANCC join the complex; phosphorylation of FANCA would induce its translocation into the nucleus.This FA complex translocates into the nucleus, where FANCE and...
متن کاملDeficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer.
Patients with the rare genetic disease, Fanconi anemia (FA), are highly susceptible to squamous cell carcinomas arising at multiple anatomic sites including the head and neck region. Human papillomaviruses (HPVs), particularly HPV16, are associated with ∼20% of head and neck squamous cell carcinomas (HNSCCs) in the general population. Some but not other investigators have reported that HNSCCs i...
متن کاملBeyond heredity mutations: alterations in the Fanconi anemia/BRCA pathway and its role in ovarian tumorigenesis
The Fanconi anemia (FA)/BRCA pathway consists of fifteen proteins that mediate DNA homologous recombination (HR) and promote chromosomal stability. Here we review the evidence that genetic and epigenetic alterations in BRCA2 (FANCD1), BRIP1 (FANCJ), FANCD2, FANCF, PALB2 (FANCN) and RAD51C (FANCO), render ovarian cells susceptible to malignant transformation. In addition, we discuss the paradoxi...
متن کاملThe FA Core Complex Contains a Homo-dimeric Catalytic Module for the Symmetric Mono-ubiquitination of FANCI-FANCD2
Activation of the main DNA interstrand crosslink repair pathway in higher eukaryotes requires mono-ubiquitination of FANCI and FANCD2 by FANCL, the E3 ligase subunit of the Fanconi anemia core complex. FANCI and FANCD2 form a stable complex; however, the molecular basis of their ubiquitination is ill defined. FANCD2 mono-ubiquitination by FANCL is stimulated by the presence of the FANCB and FAA...
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تاریخ انتشار 2015