An internal segment (residues 58–119) of the hepatitis B virus X protein is sufficient to activate MAP kinase pathways in mouse liver

FEBS Letters

Goswami, Shyamal K.¹  Nijhara, Ruchika³  Kumar, Vijay²  Jana, Siddhartha S.³  Sarkar, Debi P.³ 

[1] School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India;Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India;Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi 110021, India

关键词: Activator protein-1;    Extracellular signal-regulated kinase;    Hepatitis B virus;    Hepatitis B virus X protein;    c-Jun N-terminal kinase;    Mitogen-activated protein kinase;    AP-1;    activator protein-1;    ERK;    extracellular signal-regulated kinase;    HBV;    hepatitis B virus;    HBx;    hepatitis B virus X protein;    JNK;    c-Jun N-terminal kinase;    MAPK;    mitogen-activated protein kinase;    MEK;    MAP kinase kinase kinase;    NLS;    nuclear localization signal;    RSV-LTR;    Rous sarcoma virus long terminal repeat;   

DOI  :  10.1016/S0014-5793(01)02773-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The human hepatitis B virus X protein (HBx) is known as a dual-specificity transactivator stimulating the transcriptional machinery in the nucleus and signal transduction pathways in the cytoplasm. HBx-induced activation of mitogen-activated protein kinase (MAPK) signaling cascades is considered to play an important role in hepatitis B virus-mediated hepatocarcinogenesis. Herein, we have identified the regions of HBx that are crucial for activating such signaling cascades in vivo. A truncated mutant incorporating regions C–E (amino acids 58–140) was as effective as the full-length HBx in activating MAPKs and enhancing activator protein-1 binding activity. While deletion of region C (amino acids 58–84) or D (amino acids 85–119) led to a drastic loss of function, region E (amino acids 120–140) was dispensable for the activation of signaling cascades. Overall, these findings provide the first evidence for the requirement of domain 58–119 of HBx in transmitting mitogenic signals to the nucleus in vivo.

【 授权许可】

Unknown