5.9
CiteScore
5.9
Impact Factor
Volume 35 Issue 12
Dec.  2008
Turn off MathJax
Article Contents

Identification of karyopherin-alpha 2 as an Oct4 associated protein

doi: 10.1016/S1673-8527(08)60227-1
More Information
  • Corresponding author: E-mail address: yjin@sibs.ac.cn (Ying Jin)
  • Received Date: 2008-03-27
  • Accepted Date: 2008-10-08
  • Rev Recd Date: 2008-10-04
  • Available Online: 2008-12-23
  • Publish Date: 2008-12-20
  • The POU domain transcription factor Oct4 is a master regulator in maintaining self-renewal and pluripotency of embryonic stem (ES) cells. To further explore the functional network of Oct4, the yeast two-hybrid system was used to search for Oct4 interacting proteins. PH domain (containing POU domain and homeodomain) of human OCT4 was used as a bait. From the human testis cDNA library, we identified a strong interaction between OCT4 and karyopherin-alpha 2 (KPNA-2). KPNA2 is involved in active nuclear import of proteins. This finding was confirmed by glutathione S-transferase pull-down and co-immunoprecipitation assays. The interaction between OCT4 and KPNA-2 was further mapped to multiple regions of the two proteins. In addition, we studied nuclear localization signal (NLS) of mouse Oct4 and demonstrated that it is essential for Oct4 nuclear localization. Thus, our data suggest that Oct4 nuclear localization may be mediated by its interaction with KPNA-2.
  • loading
  • [1]
    Avilion, A.A., Nicolis, S.K., Pevny, L.H. et al. Multipotent cell lineages in early mouse development depend on SOX2 function Genes Dev., 17 (2003),pp. 126-140
    [2]
    Benetti, R., Del Sal, G., Monte, M. et al. The death substrate Gas2 binds m-calpain and increases susceptibility to p53-dependent apoptosis EMBO J., 20 (2001),pp. 2702-2714
    [3]
    Brehm, A., Ovitt, C.E., Scholer, H.R. Oct-4: More than just a POUerful marker of the mammalian germline? Apmis, 106 (1998),pp. 114-124
    [4]
    Chambers, I., Colby, D., Robertson, M. et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells Cell, 113 (2003),pp. 643-655
    [5]
    Chook, Y.M., Blobel, G. Karyopherins and nuclear import Curr. Opin. Struct. Biol., 11 (2001),pp. 703-715
    [6]
    Guo, Y., Costa, R., Ramsey, H. et al. The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression Proc. Natl. Acad. Sci. USA, 99 (2002),pp. 3663-3667
    [7]
    Hanna, L.A., Foreman, R.K., Tarasenko, I.A. et al. Requirement for Foxd3 in maintaining pluripotent cells of the early mouse embryo Genes Dev., 16 (2002),pp. 2650-2661
    [8]
    Hicks, G.R., Raikhel, N.V. Protein import into the nucleus: An integrated view Annu. Rev. Cell Dev. Biol., 11 (1995),pp. 155-188
    [9]
    Jin, Y., Xu, X.L., Yang, M.C. et al. Cell cycle-dependent colocalization of BARD1 and BRCA1 proteins in discrete nuclear domains Proc. Natl. Acad. Sci. USA, 94 (1997),pp. 12075-12080
    [10]
    Lange, A., Mills, R.E., Lange, C.J. et al. Classical nuclear localization signals: Definition, function, and interaction with importin alpha J. Biol. Chem., 282 (2007),pp. 5101-5105
    [11]
    Matsuda, T., Nakamura, T., Nakao, K. et al. STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells EMBO J., 18 (1999),pp. 4261-4269
    [12]
    Mitsui, K., Tokuzawa, Y., Itoh, H. et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells Cell, 113 (2003),pp. 631-642
    [13]
    Nakielny, S., Dreyfuss, G. Transport of proteins and RNAs in and out of the nucleus Cell, 99 (1999),pp. 677-690
    [14]
    Nichols, J., Zevnik, B., Anastassiadis, K. et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4 Cell, 95 (1998),pp. 379-391
    [15]
    Niwa, H. Molecular mechanism to maintain stem cell renewal of ES cells Cell Struct. Funct., 26 (2001),pp. 137-148
    [16]
    Niwa, H., Miyazaki, J., Smith, A.G. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells Nat. Genet., 24 (2000),pp. 372-376
    [17]
    Pan, G., Qin, B., Liu, N. et al. Identification of a nuclear localization signal in OCT4 and generation of a dominant negative mutant by its ablation J. Biol. Chem., 279 (2004),pp. 37013-37020
    [18]
    Pan, G.J., Chang, Z.Y., Scholer, H.R. et al. Stem cell pluripotency and transcription factor Oct4 Cell Res., 12 (2002),pp. 321-329
    [19]
    Raz, R., Lee, C.K., Cannizzaro, L.A. et al. Essential role of STAT3 for embryonic stem cell pluripotency Proc. Natl. Acad. Sci. USA, 96 (1999),pp. 2846-2851
    [20]
    Roach, M.L., McNeish, J.D. Methods for the isolation and maintenance of murine embryonic stem cells Methods Mol. Biol., 185 (2002),pp. 1-16
    [21]
    Sun, B.W., Yang, A.C., Feng, Y. et al. Temporal and parental-specific expression of imprinted genes in a newly derived Chinese human embryonic stem cell line and embryoid bodies Hum. Mol. Genet., 15 (2006),pp. 65-75
    [22]
    Xu, H.M., Liao, B., Zhang, Q.J. et al. Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination J. Biol. Chem., 279 (2004),pp. 23495-23503
    [23]
    Yasuhara, N., Shibazaki, N., Tanaka, S. et al. Triggering neural differentiation of ES cells by subtype switching of importin-alpha Nat. Cell Biol., 9 (2007),pp. 72-79
    [24]
    Yeom, Y.I., Fuhrmann, G., Ovitt, C.E. et al. Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells Development, 122 (1996),pp. 881-894
    [25]
    Zannini, L., Lecis, D., Lisanti, S. et al. Karyopherin-alpha2 protein interacts with Chk2 and contributes to its nuclear import J. Biol. Chem., 278 (2003),pp. 42346-42351
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (89) PDF downloads (0) Cited by ()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return