Molecular Coevolution of Nuclear and Nucleolar Localization Signals inside the Basic Domain of HIV-1 Tat.

During evolution, viruses had to adapt to an increasingly complex environment of eukaryotic cells. Viral proteins that need to enter the cell nucleus or associate with nucleoli possess nuclear localization signals (NLSs) and nucleolar localization signals (NoLSs) for nuclear and nucleolar accumulation, respectively. As viral proteins are relatively small, acquisition of novel sequences seems to be a more complicated task for viruses than for eukaryotes.

Down-regulation of A20 promotes immune escape of lung adenocarcinomas.

Inflammation is a well-known driver of lung tumorigenesis. One strategy by which tumor cells escape tight homeostatic control is by decreasing the expression of the potent anti-inflammatory protein tumor necrosis factor alpha-induced protein 3 (TNFAIP3), also known as A20. We observed that tumor cell intrinsic loss of A20 markedly enhanced lung tumorigenesis and was associated with reduced CD8 T cell-mediated immune surveillance in patients with lung cancer and in mouse models.

Origin of the nuclear proteome on the basis of pre-existing nuclear localization signals in prokaryotic proteins.

Background: The origin of the selective nuclear protein import machinery, which consists of nuclear pore complexes and adaptor molecules interacting with the nuclear localization signals (NLSs) of cargo molecules, is one of the most important events in the evolution of eukaryotic cells. How proteins were selected for import into the forming nucleus remains an open question.

Results: Here, we demonstrate that functional NLSs may be integrated in the nucleotide-binding domains of both eukaryotic and prokaryotic proteins and may coevolve with these domains.

Tat basic domain: A "Swiss army knife" of HIV-1 Tat?

Tat (transactivator of transcription) regulates transcription from the HIV provirus. It plays a crucial role in disease progression, supporting efficient replication of the viral genome. Tat also modulates many functions in the host genome via its interaction with chromatin and proteins.

Heterochromatin restricts the mobility of nuclear bodies.

Nuclear bodies are relatively immobile organelles. Here, we investigated the mechanisms underlying their movement using experimentally induced interphase prenucleolar bodies (iPNBs). Most iPNBs demonstrated constrained diffusion, exhibiting infrequent fusions with other iPNBs and nucleoli.