The discovery of a Werner helicase interacting protein (WHIP) association with the nuclear pore complex

• Published in: Cell cycle (Georgetown, Tex.) Vol. 9; no. 15; pp. 3178 - 3183
• Main Authors: Kaur, Simarna, White, Tommy E., DiGuilio, Amanda L., Glavy, Joseph S
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.08.2010
• Subjects: Animals; ATPases Associated with Diverse Cellular Activities; Binding; Biology; Bioscience; Calcium; Cancer; Carrier Proteins - metabolism; Cell; Cell Cycle; Cycle; DNA-Binding Proteins - metabolism; HeLa Cells; Humans; Immunoblotting; Landes; Nuclear Envelope - metabolism; Nuclear Pore - metabolism; Organogenesis; Protein Binding; Proteins; Rats; Small Ubiquitin-Related Modifier Proteins - metabolism
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.9.15.12524

The gateway for molecular trafficking between the cytoplasm and the nucleus is the Nuclear Pore Complex (NPC). Through mass spectral analysis of the isolated Nuclear Pore Nup107-160 subcomplex, we discovered an in vivo interaction with Werner's Helicase Interacting Protein 1, (WRNIP1 or WHIP). WHIP was originally identified as a binding partner of Werner protein (WRN), which functions to maintain genome stability and is responsible for the progeria disease, Werner syndrome. We established the reciprocal isolation of Nup107 by α-WHIP. WHIP was found in purified Nuclear Envelope (NE) fractions treated with DNase/RNase/Heparin. We demonstrated by immunofluorescence microscopy that WHIP is located at the nuclear rim as well as punctate regions in the nuclear matrix. Ultimately, synchronized cells show a dynamic association between WHIP and the Nup107-160 subcomplex through the cell cycle without an interaction with WRN. We thus identify WHIP as a partner/component of the NE/NPC and set forth to investigate a role for the protein positioned at the NPC.