Functions of WW domains in the nucleus

FEBS Letters

Sudol, Marius²  Sliwa, Krzysztof³  Russo, Tommaso¹ 

[1] Department of Biochemistry and Medical Biotechnology, University of Naples, ‘Federico II’, Naples I-80131, Italy;Department of Medicine, Mount Sinai Medical Center, New York, NY 10029, USA;Department of Physics and Astronomy, Tufts University, Medford, MA 02155, USA

关键词: Protein–protein interaction;    WW domain;    Carboxy-terminal domain of RNA polymerase II;    Phosphorylation;    O-Glycosylation;    cis/trans Conformation;    Alzheimer's disease;    Tau protein;    Fe65 adapter protein;    cdk;    cyclin-dependent kinase;    CTD;    carboxy-terminal domain;    K;    lysine;    L;    leucine;    MPM-2;    mitotic phosphoprotein monoclonal-2;    NLS;    nuclear localization signal;    P;    proline;    R;    arginine;    RNA Pol II;    RNA polymerase II large subunit;    S;    serine;    SH3;    Src homology domain 3;    a protein module originally identified by homology to the amino-terminal region of Src protein;    T;    threonine;    W;    tryptophan;    WW;    a protein module with two conserved Ws;    Y;    tyrosine;    YAP;    Yes kinase-associated protein;    x;    any amino acid;   

DOI  :  10.1016/S0014-5793(01)02122-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The WW domain is a protein module found in a wide range of signaling proteins. It is one of the smallest protein modules that folds as a monomer without disulfide bridges or cofactors. WW domains bind proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. Although the WW domain was initially considered a ‘cytoplasmic module’, the proteins containing WW domains have also been localized in the cell nucleus. Moreover, these proteins have been documented to participate in co-activation of transcription and modulation of RNA polymerase II activity. The carboxy-terminal domain (CTD) of RNA polymerase II acts as an assembly platform for distinct WW domain-containing proteins that affect the function of the RNA polymerase II. The formation of complexes between CTD and WW domain-containing proteins is regulated by phosphorylation of the CTD. Since the CTD sequence is highly repetitive and a target of several post-translational modifications and conformational changes, it presents a unique structure capable of enormous molecular diversity. The WW domain has been implicated in several human diseases including Alzheimer's disease. The WW domain-containing iso-prolyl isomerase named Pin1, a protein known to be essential for cell cycle progression, was shown to be active in restoration of the microtubule-binding activity of Tau, a protein of neurofibrillar tangles found in the brains of Alzheimer's patients. It is the WW domain of Pin1 that interacts directly with Tau protein. In addition, the WW domain-containing adapter protein FE65 was shown to regulate processing of Alzheimer's amyloid precursor protein. It is expected that by understanding the details of the WW domain-mediated protein–protein interactions, we will be able to illuminate numerous signaling pathways which control certain aspects of transcription and cell cycle.

【 授权许可】

Unknown