Cell-cycle regulation and dynamics of cytoplasmic compartments containing the promyelocytic leukemia protein and nucleoporins

• Published in: Journal of cell science Vol. 122; no. 8; pp. 1201 - 1210
• Main Authors: Jul-Larsen, Åsne, Grudic, Amra, Bjerkvig, Rolf, Ove Bøe, Stig
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 15.04.2009
• Subjects: Cell Cycle - drug effects; CREB-Binding Protein - metabolism; Cytoplasm - drug effects; Cytoplasm - metabolism; G1 Phase; HeLa Cells; Humans; Microtubules - metabolism; Mitosis; Nocodazole - pharmacology; Nuclear Envelope - metabolism; Nuclear Localization Signals - metabolism; Nuclear Pore Complex Proteins - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oncogene Proteins, Fusion - metabolism; Promyelocytic Leukemia Protein; Protein Transport; Recombinant Fusion Proteins - metabolism; RNA Interference; RNA, Small Interfering - metabolism; Time Factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transfection; Tubulin Modulators - pharmacology; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.040840

Nucleoporins and the promyelocytic leukemia protein (PML) represent structural entities of nuclear pore complexes and PML nuclear bodies, respectively. In addition, these proteins might function in a common biological mechanism, because at least two different nucleoporins, Nup98 and Nup214, as well as PML, can become aberrantly expressed as oncogenic fusion proteins in acute myeloid leukemia (AML) cells. Here we show that PML and nucleoporins become directed to common cytoplasmic compartments during the mitosis-to-G1 transition of the cell cycle. These protein assemblies, which we have termed CyPNs (cytoplasmic assemblies of PML and nucleoporins), move on the microtubular network and become stably connected to the nuclear membrane once contact with the nucleus has been made. The ability of PML to target CyPNs depends on its nuclear localization signal, and loss of PML causes an increase in cytoplasmic-bound versus nuclear-membrane-bound nucleoporins. CyPNs are also targeted by the acute promyelocytic leukemia (APL) fusion protein PML-RARα and can be readily detected within the APL cell line NB4. These results provide insight into a dynamic pool of cytoplasmic nucleoporins that form a complex with the tumor suppressor protein PML during the G1 phase of the cell cycle.