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ARNT isoforms differentially regulate cancer cell growth through a p53-dependent mechanism.
textAryl hydrocarbon receptor nuclear translocator (ARNT) is an important player in xenobiotic and hypoxic responses. In addition to this, my mentor has shown that ARNT is an integral cofactor of NF-kB signaling. However, these initial observations of ARNT-mediated NF-kB modulation were based on simultaneous suppression of the two ARNT isoforms, isoform 1 and 3, and therefore precluded the isolated examination of each isoform’s function. We show here that lymphoid malignancies exhibit higher levels of ARNT isoform 1 compared to ARNT isoform 3. However, normal T and B lymphocytes are seen to harbor equal levels of ARNT isoform 1 and 3. We hypothesize that the increase in ARNT isoform 1 is necessary for the growth of these cancer cells as suppression of isoform 1 resulted in S-phase cell cycle arrest. These findings reveal that ARNT isoform 1 potentiates cell growth by antagonizing a p53 cell cycle inhibitory mechanism and this further suggests that ARNT targeted therapies would benefit chemotherapy regimens.Cellular and Molecular Biolog
Analysis of HLA association among North Indian HIV-positive individuals co-infected with Mycobacterium tuberculosis
Background: Genetic variation in HLA genes influence the immune response and may thus contribute to differential development of tuberculosis (TB) in HIV-infected individuals. The study was designed to determine whether HLA polymorphisms influence the development of Mycobacterium tuberculosis infection in HIV-infected individuals. Materials and Methods: Fifty HIV-positive individuals without TB (HIV+TB−), 50 HIV patients co-infected with TB (HIV+TB+) and 50 control subjects (HIV-TB-) were analyzed for HLA Class I and II polymorphisms. Results: In HLA Class II, frequency of occurrence of DRB1*13 (OR 3.165, CI 1.176–8.518, P value 0.019), DRB5 (OR 2.253, CI 1.011–5.019, P value 0.045) and DQB1*06 (OR 2.705, CI 1.197–6.113, P value 0.016) were increased in HIV+TB+compared to HIV+TB−. HLA DQB1*02 (OR 0.436, CI 0.185–1.029, P value 0.05) on the other hand conferred a protective role. In HLA Class I, frequency of B*15 (OR 2.705, CI 1.040–7.036, P value 0.038) was increased, whereas B*51 (OR 0.148, CI 0.031–0.706, P value 0.007) was decreased in HIV+TB+group compared to HIV+TB−. These differences however were not significant when compared with healthy controls. Conclusion: HLA polymorphisms independently did not account for the susceptibility to either of the disease mostly, although they seem to play a role once the infection(s) has established in a particular individual. Further studies are needed on a larger sample size to confirm these observations