Skip NavigationSkip to Content
Return Return to Search Results

Tuberous sclerosis complex 2 gene product interacts with human SMAD proteins - A molecular link of two tumor suppressor pathways

  1. Author:
    Birchenall-Roberts, M. C.
    Fu, T.
    Bang, O. S.
    Dambach, M.
    Resau, J. H.
    Sadowski, C. L.
    Bertolette, D. C.
    Lee, H. J.
    Kim, S. J.
    Ruscetti, F. W.

  2. Author Address

    NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. Van Andel Inst, Grand Rapids, MI 49506 USA. NCI Frederick, Expt Immunol Lab, Frederick, MD 21702 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Birchenall-Roberts, MC, NCI, SAIC Frederick, Basic Res Program, POB B,Bldg 567-259, Frederick, MD 21702 USA
    1. Year: 2004
  2. Journal: Journal of Biological Chemistry
    1. 279
    2. 24
    3. Pages: 25605-25613
  4. Type of Article: Article
  1. Abstract:

    Tuberin (TSC2) is a tumor suppressor gene. At the cellular level, tuberin is required as a critical regulator of cell growth, neuronal differentiation (Soucek, T., Holzl, G., Bernaschek, G., and Hengstschlager, M. (1998) Oncogene 16, 2197-2204), and tumor suppression (Crino, P. B., and Henske, E. P. (1999) Neurology 53, 1384-1390). Here we report a critical role for tuberin in late stage myeloid cell differentiation. Tuberin strongly augments transforming growth factor (TGF)-beta1 signal transduction pathways, including SMAD activation. We also demonstrate that the amino-terminal region of tuberin interacts specifically with the MH2 domain of SMAD2 and SMAD3 proteins to regulate TGF-beta1-responsive genes such as p21(CIP). Inhibition of tuberin expression by Tsc2 antisense greatly reduces the ability of TGF-beta to transcriptionally regulate p21(CIP), p27(KIP), and cyclin A leading to an abrogation of the antiproliferative effects of TGF-beta1. Also, inhibition of tuberin expression during stimulation of monocytic differentiation with vitamin D-3 and TGF-beta1 significantly impaired myeloid cell growth inhibition and differentiation. Together, the data demonstrate the presence of a novel activation process following TGF-beta1 stimulation that requires tuberin-dependent activity

    See More

  1. Keywords:

External Sources

  1. No sources found.

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel