The differentiation of several T and B cell effector programs in the immune system is directed by signature transcription factors that induce rapid epigenetic remodeling. We report that PLZF, the BTB-ZF transcription factor directing the innate-like effector program of NKT thymocytes 1,2 was prominently associated with cullin 3 (Cul3), an E3 ubiquitin ligase previously shown to use BTB domain-containing proteins as adaptors for substrate binding 3–7. PLZF transported Cul3 to the nucleus where the two proteins were associated within a chromatin modifying complex. Furthermore, PLZF expression resulted in selective changes of ubiquitination of multiple components of this complex. Cul3 was also found associated with another BTB-ZF transcription factor, Bcl6, which directs the B cell germinal center and the T follicular helper programs. Conditional deletion in mice demonstrated an essential role of Cul3 for the development of PLZF- and Bcl6-dependent lineages. We conclude that distinct lineage-specific BTB-ZF transcription factors recruit Cul3 to alter the ubiquitination pattern of their associated chromatin modifying complex. We propose that this novel function is essential to direct the differentiation of several T and B lymphocyte effector programs, and may also be involved in the oncogenic role of PLZF and Bcl6 in leukemias and lymphomas 8,9.
We systematically reviewed the literature on anal human papillomavirus (HPV) infection, dysplasia, and cancer among Black and White men who have sex with men (MSM) to determine if a racial disparity exists. We searched 4 databases for articles up to March 2014. Studies involving Black MSM are nearly absent from the literature. Of 25 eligible studies, 2 stratified by race and sexual behavior. Both reported an elevated rate of abnormal anal outcomes among Black MSM. White MSM had a 1.3 times lower prevalence of group-2 HPV (P < .01) and nearly 13% lower prevalence of anal dysplasia than did Black MSM. We were unable to determine factors driving the absence of Black MSM in this research and whether disparities in clinical care exist. Elevated rates of abnormal anal cytology among Black MSM in 2 studies indicate a need for future research in this population.
Lead organizations such as UCM were able to assist and oversee HIV screening and linkage to care for HIV patients diagnosed at community sites. HIV screening and linkage to care can be accomplished by incorporating standard testing for HIV into routine medical care.
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