title: Kaposi's sarcoma-associated herpesvirus lana2 protein interacts with the pocket proteins and inhibits their sumoylation.
abstract: The pocket proteins retinoblastoma protein (pRb), p107 and p130 are the key targets of oncoproteins expressed by DNA tumor viruses. Some of these viral proteins contain an LXCXE motif that mediates the interaction with the three pocket proteins and the inhibition of the pRb SUMOylation. Kaposi's sarcoma herpesvirus (KSHV) contains at least two proteins that can regulate pRb function but, so far, a KSHV-encoded protein targeting p107 and p130 has not been identified. Here, we show that the KSHV latent protein LANA2 binds to pRb, p107 and p130. LANA2 contains an LXCXE motif that is required for bypassing pRb-mediated cell-cycle arrest and for inhibiting pRb SUMOylation. Finally, we demonstrate that, in addition to pRb, both p107 and p130 can be SUMOylated, and this modification is also inhibited by LANA2 in an LXCXE-dependent manner. These results demonstrate, for the first time, the SUMOylation of p107 or p130 and, so far, they represent the first example of a KSHV protein able to interact with the three pocket proteins and to inhibit their conjugation to SUMO.
authors: Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, Madrid, Spain.
authors: L
authors: L
authors: Marcos-Villar
authors: Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, Madrid, Spain.
authors: P
authors: P
authors: Gallego
authors: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors: C
authors: C
authors: Muñoz-Fontela
authors: Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, Madrid, Spain.
authors: C F
authors: CF
authors: de la Cruz-Herrera
authors: Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, Madrid, Spain.
authors: M
authors: M
authors: Campagna
authors: Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, Madrid, Spain.
authors: D
authors: D
authors: González
authors: Proteomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Buildin Derio, Spain.
authors: F
authors: F
authors: Lopitz-Otsoa
authors: 1] Proteomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Buildin Derio, Spain [2] Ubiquitylation and Cancer Molecular Biology laboratory, Inbiomed, San Sebastian-Donostia, Gipuzkoa, Spain.
authors: M S
authors: MS
authors: Rodríguez
authors: Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, Madrid, Spain.
authors: C
authors: C
authors: Rivas
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D019288:Herpesvirus 8, Human / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107 / Q000378:metabolism*; D058207:Sumoylation; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D050835:Interferon Regulatory Factors; C493844:RBL1 protein, human; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D014764:Viral Proteins; C413486:viral interferon regulatory factors