Investigation of molecular biology of leukaemia inhibitory factor (LIF): A Bioinformatics approach

Paper Details

Research Paper 01/06/2011
Views (322) Download (4)

Investigation of molecular biology of leukaemia inhibitory factor (LIF): A Bioinformatics approach

Sanuwarul Kabir, Abdullah-Al-Emran, Zinnia Naoshin, Farzana Ahmed
Int. J. Biosci.1( 3), 20-28, June 2011.
Certificate: IJB 2011 [Generate Certificate]


Leukaemia inhibitory factor (LIF) is a glycoprotein with a variety of functions in different organ systems. It has great impact on embryogenic stem cell as it is required to maintain the differentiated state of a cell. In our study we tried to find out various molecular features of LIF in human such as conserved domains, important transcription factors, sequence motifs, protein motifs, conserved miRNA binding site and single nucleotide polymorphisms with the help of bioinformatics tools. We also tried to generate a generalized downstream signaling pathway for LIF. These findings could be used to control the expression of LIF for treatment and better drug designing.


Arici A, Engin O, Attar E. 1995. Modulation of leukaemia inhibitory factor gene expression and protein biosynthesis in human endometrium. J. Clin. Endocrinol. Metab. 80, 1908–1915.

Baumann H and Wong GG. 1989. Hepatocyte-stimulating factor III shares structural and functional identity with leukemia-inhibitory factor. J. Immunol. 143, 1163-1167.

Chakravarti A. 2001. Single nucleotide polymorphisms: to a future of genetic medicine. Nature 409, 822-823.

Dunglinson GF, Barlow DH, Sargent IL. 1996. Leukaemia inhibitory factor significantly enhances the blastocyst formation rates of human embryos cultured in serum-free medium. Hum. Reprod. 11, 191–196

Dhaeseleer P. 2006. What are DNA sequence motifs? Nature Biotechnology 24, 423 – 425.

Gearing DP, Comeau MR, Friend DJ, Gimpel SD, Thut CJ, McGourty J, Brasher KK. 1992. The IL-6 signal transducer, gp130: an oncostatin receptor and affinity converter for the LIF receptor. Science 255, 1434–1437.

Gearing DP, Gough, NM, King JA, Hilton DJ, Nicola NA, Simpson RJ, Nice EC, Metcalf D. 1987. Molecular cloning and expression of cDNA encoding a murine myeloid leukemia inhibitory factor (LIF). EMBO J. 6, 3395-4007.

Hilton DJ, Nicola NA, Gough NM, Metcalf D. 1988. Resolution of three distinct factors produced by Krebs ascites cells which have differentiation – including activity on murine myeloid leukemia cell lines. J. Biol. Chem. 263, 9238 – 9243

Imoedemhe, D.A., Sigue, A.B., Pacpaco, E.L. 1995. A comparative analysis of embryos derived from routine in-vitro fertilization and subzonal microinsemination. Hum. Reprod. 10, 2970–2975.

Kola I, Davey A, Gough NM. 1990. Localization of the murine leukemia inhibitory factor gene near the centromere on chromosome 11. Growth Factors 2, 235-240.

Koonin EV. 2005. Orthologs, paralogs, and evolutionary genomics. Annu Rev Genet. 39, 309-38.

Koonin EV, Galperin Michael Y, Norwell MA. 2003. Sequence-Evolution – Function Computational Approaches in Comparative Genomics, Kluwer Academic Publishers.

Malek JA and Haft DH. 2001. Conserved protein domains are maintained in an average ratio to proteome size. Genome Biology 2, 80-90.

Metcalf D. 1992. Leukemia Inhibitory Factor-A Puzzling Polyfunctional Regulator. Growth Factors 7, 169-173.

Metcalf D and Gearing DP. 1990. A myelosclerotic syndrome in mice engrafted with cells producing high levels of leukemia inhibitory factor (LIF). Leukemia 3, 847-852

Mori M, Yamaguchi K, Abe K. 1989. Purification of a lipoprotein lipase-inhibiting protein produced by a melanoma cell line associated with cancer cachexia. Biochem. Biophys. Res. Commun. 160, 1085-1092.

Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, Taga T & Kishimoto T. 1993. IL-6 induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science 260, 1808–1810.

Nachtigall MJ, Kliman HJ, Feinberg RF. 1996. The effect of leukaemia inhibitory factor (LIF) on trophoblast differentiation: A potential role in human implantation. J. Clin. Endocrinol. Metab. 81, 801– 806.

Okita K and Yamanaka S. 2006. Intracellular signaling pathways regulating pluripotency of embryonic stem cells. Curr Stem Cell Res Ther. 1(1), 103-11.

Sandve GK and Finn DF. 2006. A survey of motif discovery methods in an integrated framework. Biology Direct 1, 11.

Smith AG, Heath JK, Donaldson DD. 1988. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336, 688-690.

Stoneking M. 2001. Single nucleotide polymorphisms: from the evolutionary past Nature 409, 821-822.

Sutherland GR, Baker E, Hyland VJ, Callen DF. 1989. The gene for human leukemia inhibitory factor (LIF) maps to 22q12. Leukemia 3, 9-13.

Taga T and Kishimoto T. 1992. Cytokine receptors and signal transduction. FASEB Journal 6, 3387–3396.

Tomida M., Yamamoto-Yamaguchi Y, Hozumi M. 1984. Purification of a factor inducing differentiation of mouse myeloid leukemic M1 cells from conditioned medium of mouse fibroblast L929 cells. J. Biol. Chem. 259, 10978-10982

Vogiags D and Salamonsen LA. 1999. The role of leukaemia inhibitory factor in the establishment of pregnancy. J Endocrinol. 160(2), 181-90.

Van der Elst J, van den Abbeel E, Camus M. 1996. Long-term evaluation of implantation of fresh and cryopreserved human embryos following ovarian stimulation with buserelin acetate-human menopausal gonadotrophin (HMG) or clomiphene citrate-HMG. Hum. Reprod. 11, 2097–2106.

Williams RL, Hilton DJ, Pease S. 1988. Myeloid leukemia inhibitory factor (LIF) maintains the developmental potential of embryonic stem cells. Nature 336, 684-687.

Yamamori T, Fukada K, Aebersold R, Korsching S, Fann MJ.  1989. The  cholinergic neuronal  differentiation  factor  from  heart  cells  is identical to leukemia inhibitory factor. Science 246, 1412-1416.

Yue   Xu,   Xiuwen    Zhu,    Heung    Sik   Hahm, Wanguo Wei, Ergeng Hao. 2010. Revealing  a core signaling regulatory mechanism for pluripotent stem cell survival and self-renewal by small molecules. Proc Natl Acad Sci U S A. 2010 May 4.