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Molecular and Cellular Biology, July 2008, p. 4629-4641, Vol. 28, No. 14
0270-7306/08/$08.00+0     doi:10.1128/MCB.00120-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Nuclear Factor 45 (NF45) Is a Regulatory Subunit of Complexes with NF90/110 Involved in Mitotic Control ^,

Deyu Guan,¹ Nihal Altan-Bonnet,³ Andrew M. Parrott,¹ Cindy J. Arrigo,^1, Quan Li,¹ Mohammed Khaleduzzaman,^1, Hong Li,¹ Chee-Gun Lee,¹ Tsafi Pe'ery,^1,2 and Michael B. Mathews^1*

Departments of Biochemistry and Molecular Biology,¹ Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, P.O. Box 1709, Newark, New Jersey 07103-1709,² Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102³

Received 22 January 2008/ Returned for modification 29 February 2008/ Accepted 28 April 2008

Nuclear factor 90 (NF90) and its C-terminally extended isoform, NF110, have been isolated as DNA- and RNA-binding proteins together with the less-studied protein NF45. These complexes have been implicated in gene regulation, but little is known about their cellular roles and whether they are redundant or functionally distinct. We show that heterodimeric core complexes, NF90-NF45 and NF110-NF45, exist within larger complexes that are more labile and contain multiple NF90/110 isoforms and additional proteins. Depletion of the NF45 subunit by RNA interference is accompanied by a dramatic decrease in the levels of NF90 and NF110. Reciprocally, depletion of NF90 but not of NF110 greatly reduces the level of NF45. Coregulation of NF90 and NF45 is a posttranscriptional phenomenon, resulting from protein destabilization in the absence of partners. Depletion of NF90-NF45 complexes retards cell growth by inhibition of DNA synthesis. Giant multinucleated cells containing nuclei attached by constrictions accumulate when either NF45 or NF90, but not NF110, is depleted. This study identified NF45 as an unstable regulatory subunit of NF90-NF45 complexes and uncovered their critical role in normal cell division. Furthermore, the study revealed that NF90 is functionally distinct from NF110 and is more important for cell growth.

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* Corresponding author. Mailing address: Phone: (973) 972-4411. Fax: (973) 972-5594. E-mail: mathews{at}umdnj.edu

Published ahead of print on 5 May 2008.

Supplemental material for this article may be found at http://mcb.asm.org/.

Present address: Department of Biology, New Jersey City University, Jersey City, NJ 07002.

Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Molecular and Cellular Biology, July 2008, p. 4629-4641, Vol. 28, No. 14
0270-7306/08/$08.00+0     doi:10.1128/MCB.00120-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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