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The transforming growth factor-1 (TGF-1) is a cytokine involved in many biological events inlcuding immunosuppression, angiogenesis, cell growth, and apoptosis. Expression of TGF-1 at the transcriptional level is controlled by a series of ubiquitous and specialized factors whose activities can be modulated by a variety of signaling events. Here we demonstrate that activity of the TGF-1 promoter is increased by C/EBP, a DNA-binding transcription factor whose activity can be influenced by several immunomodulators, in astrocytes and microglial cells. Interestingly, expression of Smad3 and Smad4, the downstream regulators of the TGF-1-signaling pathway, impairs the activity of C/EBP on the TGF-1 promoter. Further, we demonstrate that MH2, a common domain among Smads that has protein-binding activities, interacts with C/EBP and decreases its association with a region of the TGF-1 promoter that is responsive to C/EBP activation. Interestingly, the p65 subunit of nuclear factor-B (NF-B), which also interacts with C/EBP, cooperates with MH2 and decreased DNA-binding and transcriptional activities of C/EBP on the TGF-1 promoter. These observations indicate that an autoregulatory mechanism, involving the MH2 domain of Smads, modulates activation of the TGF-1 promoter by C/EBP. Further, our results show that the interplay between NF-B and C/EBP has an impact on the ability of C/EBP to stimulate TGF-1 transcription, hence, suggesting that the cross-communication of signaling pathways that modulate NF-B and C/EBP may dictate the level of TGF-1 promoter activity. [ABSTRACT FROM AUTHOR]

Interplay of the HIV-1 regulatory protein, Tat, with several cellular factors plays an important role in transcriptional regulation of the viral promoter, the long terminal repeat (LTR). Special attention has been paid to NF-?B, a family of inducible transcription factors, which interact with a specific DNA motif within the LTR. Here, we report on the physical and functional interaction of NFBP, a recently identified protein that interacts with the P65 subunit of NF-?B, with HIV-1 Tat. NFBP colocalizes with Tat in the nucleus and nucleoli, recognizes the amino acid residues 37 to 48 of Tat, and its interaction is modulated by RNA molecules. The interaction of NFBP with Tat modulates the synergism between Tat and P65 in activating LTR transcription. In the absence of the ?B-binding sites, NFBP augments the TAR-dependent activation by Tat, yet it interferes with the synergistic effect of P65 and Tat on LTR transcription. 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The late region of the three primate polyomaviruses (JCV, BKV, and SV40) encodes a small, highly basic protein known as agnoprotein. While much attention during the last two decades has focused on the transforming proteins encoded by the early region (small and large T-antigens), it has become increasingly evident that agnoprotein has a critical role in the regulation of viral gene expression and replication, and in the modulation of certain important host cell functions including cell cycle progression and DNA repair. The importance of agnoprotein is underscored by its expression during lytic infection of glial cells by JCV that occurs in progressive multifocal leukoencephalopathy (PML), and also in some JCV-associated human neural tumors particularly medulloblastoma. In this review, we will discuss the structure and function of agnoprotein in the viral life cycle during the course of lytic infection and the consequences of agnoprotein expression for the host cell. 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]