- 作者: Wei-Kuang Liu Chia-Yi Chien Chen-Kung Chou Jin-Yuan Su
- 作者服務機構: Department of Life Science and Institute of Microbiology and Immunology, National Yang-Ming University, Department of Education and Research, Veterans General Hospital, Taipel, Taiwan, ROC
- 中文摘要: --
- 英文摘要:
The Peutz-Jeghers syndrome (PJS) is a hereditary disor-
der that predisposes an individual to benign and malig-
nant tumors in multiple organ systems. Recently, the
locus responsible for PJs was mapped genetically to the
LKB1 gene, with a subsequent investigation proving that
it is responsible for most cases of PJS. LKB1 encodes a
nuclear serine/threonine protein kinase, and potential
tumor-suppressing activity has been attributed to LKB1
kinase. However, how LKB1 exerts its tumor-suppress-
ing function remains to be determined. In this report, we
describe the identification of a putative human LKB1-
interacting protein, FLIP1, using the yeast two-hybrid
system. Two regions of the LKB1 sequence have been
determined to be crucial for the interaction with FLIP1.
FLIP1 encodes a protein of 429 amino acids with a pre-
dicted molecular weight of 47 kd. In contrast to LKB1,
which is mainly nuclear, FLIP1 is a cytoplasmic protein,
and its expression is ubiquitous in all human tissues
examined to date. Interestingly, deletion of the 195 N-
terminal amino acids allows FLIP1 to enter the nucleus,
suggesting the presence of a regulatory mechanism
through its N-terminus for nuclear entry. In addition, we
found that ectopic expression of FLIP1 selectively blocks
cytokine-induced NF-KB activation. The involvement of
FLIP1 in the regulation of NF-KB activity may shed new
light on the role of LKB1 in tumor suppression. - 中文關鍵字: --
- 英文關鍵字: FLIP1. LKB1. NF-kB inhibitor. Peutz-Jeghers syndrome. Protein Kinase. Tumor-suppressor gene