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Developmental regulation of the heat shock response by nuclear transport factor karyopherin-α3

Fang, Xiang-Dong and Chen, Tianxin and Tran, Kim and Parker, Carl S. (2001) Developmental regulation of the heat shock response by nuclear transport factor karyopherin-α3. Development, 128 (17). pp. 3349-3358. ISSN 0950-1991.

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During early stages of Drosophila development the heat-shock response cannot be induced. It is reasoned that the adverse effects on cell cycle and cell growth brought about by Hsp70 induction must outweigh the beneficial aspects of Hsp70 induction in the early embryo. Although the Drosophila heat shock transcription factor (dHSF) is abundant in the early embryo it does not enter the nucleus in response to heat shock. In older embryos and in cultured cells the factor is localized within the nucleus in an apparent trimeric structure that binds DNA with high affinity. The domain responsible for nuclear localization upon stress resides between residues 390 and 420 of the dHSF. Using that domain as bait in a yeast two-hybrid system we now report the identification and cloning of a Drosophila nuclear transport protein karyopherin-α3 (dKap-α3). Biochemical methods demonstrate that the dKap-α3 protein binds specifically to the dHSF’s nuclear localization sequence (NLS). Furthermore, the dKap-α3 protein does not associate with NLSs that contain point mutations, which are not transported in vivo. Nuclear docking studies also demonstrate specific nuclear targeting of the NLS substrate by dKap-α3. Consistant with previous studies demonstrating that early Drosophila embryos are refractory to heat shock as a result of dHSF nuclear exclusion, we demonstrate that the early embryo is deficient in dKap-α3 protein through cycle 12. From cycle 13 onward the transport factor is present and the dHSF is localized within the nucleus thus allowing the embryo to respond to heat shock.

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Additional Information:© 2001 The Company of Biologists Limited. Accepted June 15, 2001. We thank Christine Molodovich and LiJuan Wang for technical assistance. We thank Susan Ou and the Caltech Monoclonal Antibody Facility for generating the monoclonal antibodies used in this study. We thank Dr Al Courey for generously allowing us to collect staged embryos from his laboratory. We thank Dr Eric Davidson, Dr Bruce Hay, Duncan Odom, Phoebe Tzou and Dr Ebrahim Zandi for helpful comments on the manuscript. This work was supported by NIH Grant GM47381 to C.S.P.
Funding AgencyGrant Number
National Institutes of HealthGM47381
Subject Keywords:Drosophila melanogaster, dKap-α3, Heat shock factor, Nuclear transport
Issue or Number:17
Record Number:CaltechAUTHORS:FANdev01
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:12084
Deposited By: Archive Administrator
Deposited On:22 Oct 2008 20:26
Last Modified:13 Apr 2022 17:09

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