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Interaction of HCF-1 with a cellular nuclear export factor.
Shahana S Mahajan1, Markus M Little, Rafael Vazquez
1Department of Microbiology and the Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
The Journal of Biological Chemistry
|September 18, 2002
Summary
A newly identified protein, HPIP, regulates the cellular protein HCF-1 by controlling its location between the nucleus and cytoplasm. This interaction is crucial for herpes simplex virus (HSV) gene activation by VP16.
Area of Science:
- Molecular Biology
- Virology
- Cell Biology
Background:
- Host Cell Factor-1 (HCF-1) is essential for VP16-mediated activation of herpes simplex virus (HSV) immediate-early genes.
- HCF-1 also functions in cellular processes, including transcription coactivation and cell proliferation.
- VP16 and cellular transcription factor LZIP share an HCF-1 binding motif recognized by HCF-1's beta-propeller domain.
Purpose of the Study:
- To identify and characterize novel cellular proteins that interact with the HCF-1 beta-propeller domain.
- To investigate the role of a newly discovered HCF-1 binding protein, HPIP, in regulating HCF-1's subcellular localization and function.
- To elucidate the mechanism by which HPIP influences HCF-1 activity in the context of HSV infection.
Main Methods:
- Identification of HPIP as an HCF-1 beta-propeller domain binding protein.
- Analysis of HPIP's functional HCF-binding motif and leucine-rich nuclear export sequence.
- Investigation of HPIP's nucleocytoplasmic shuttling via CRM1-dependent transport.
- Assessment of HPIP's effect on HCF-1 subcellular localization upon overexpression.
Main Results:
- HPIP binds to the HCF-1 beta-propeller domain and possesses a nuclear export sequence.
- HPIP shuttles between the nucleus and cytoplasm in a CRM1-dependent manner.
- Overexpression of HPIP causes HCF-1 to accumulate in the cytoplasm, suggesting HPIP regulates HCF-1 localization.
- HPIP-mediated HCF-1 export may supply cytoplasmic HCF-1 for VP16 import into the nucleus.
Conclusions:
- HPIP is a novel regulator of HCF-1 subcellular localization.
- HPIP modulates HCF-1 activity by controlling its distribution between cellular compartments.
- HPIP-dependent cytoplasmic localization of HCF-1 may be critical for initiating HSV infection by facilitating VP16 nuclear import.