Background: [FeFe]-Hydrogenases catalyze the reversible reduction of protons to H 2 . Results: Substitution of strictly conserved amino acids in a putative proton transport pathway impairs hydrogenase activity. Conclusion: The four strictly conserved residues studied in this work are critical for hydrogenase activity and are implicated in proton transfer. Significance: Elucidating the method of intramolecular substrate transport in [FeFe]-hydrogenases is vital for understanding the enzymatic mechanism.
Loss of the Epstein-Barr virus (EBV) genome from Akata Burkitt lymphoma (BL) cells is coincident with
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirusthat establishes a life-long latent infection within B lymphocytes. Latency is associated with the expression of as many as ten viral proteins, including a family of six nuclear proteins (EBNAs), three integral membrane proteins (LMPs) and the recently identified polypeptide 24). Several of these, most notably the EBNA-3 proteins, elicit a strong EBVspecific cytotoxic T-lymphocyte immune response (23,38,43). Through differential expression of EBV proteins that are immunogenic, potentially oncogenic and those necessary for sustaining infection, an equilibrium is established between infected B cells and the host's immune surveillance. As a consequence, a relatively stable pool of latently infected cells is maintained by the host (31,36,56). Thus, EBV is particularly well adapted for persistence within B lymphocytes of an immune host, and though the virus encodes the oncogenic protein LMP-1, its association with human malignancy is rare, especially considering the high incidence of EBV infection worldwide.As a result of the balanced relationship that exists between EBV and its host, pathogenesis associated with EBV latency is
Bcl-2 family proteins are key regulators of apoptosis and function as cell death antagonists (e.g., Bcl-2, Bcl-X L , and Mcl-1) or agonists (e.g., Bax, Bad, and Bak). Here we report that among the Bcl-2 family of proteins tested (Bcl-2, Bcl-X L , Mcl-1, Bax, Bad, and Bak), Bcl-X L was unique in that its protein levels were tightly regulated by hemopoietins in both immortal and primary myeloid progenitors. Investigating signaling pathways utilized by cytokine receptors established that the regulation of Bcl-X L protein levels is mediated by the Jak kinase pathway and is independent of other signaling effectors including STATs, PI-3 kinase, and Ras. Moreover, we provide the first direct evidence that Bcl-X is altered in cancer, because bcl-X expression was activated selectively by retroviral insertions in murine myeloid and T-cell hemopoietic malignancies. Tumors harboring bcl-X insertions had altered bcl-X RNAs, expressed elevated levels of Bcl-X L protein, and lacked the requirements for cytokines normally essential for cell survival. Finally, overexpression of Bcl-X L effectively protected IL-3-dependent myeloid cells from apoptosis following removal of trophic factors. Therefore, Bcl-X L functions as a key cytokine regulated anti-apoptotic protein in myelopoiesis and contributes to leukemia cell survival.
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