This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhong, Q. Articles by Lee, W.-H. Search for Related Content PubMed Articles by Zhong, Q. Articles by Lee, W.-H.

Perturbation of TSG101 Protein Affects Cell Cycle Progression¹

Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245

tsg101 was recently identified as a tumor susceptibility gene by functional inactivation of allelic loci in mouse 3T3 fibroblasts. Although previous studies suggested that homozygous intragenic deletion of TSG101 is rare in breast cancer cells and specimens, the neoplastic phenotype caused by tsg101 inactivation implicated that tsg101 may play a significant role in cell growth control. Here, we characterize mouse polyclonal and monoclonal antibodies that specifically recognize the TSG101 protein (molecular mass, 46 kDa) in whole-cell lysates by straight Western blot analysis. By indirect immunofluorescence staining, TSG101 was found to be localized in the cytoplasm throughout the entire cell cycle. However, the nuclear staining increases from G₁ to S phase and becomes dominant in late S phase. TSG101 is mainly distributed surrounding the chromosomes during M phase. The expression level of TSG101 is not cell cycle dependent. It is possible that the relocalization of TSG101 from the cytoplasm into the nucleus may be relevant to its function. Microinjection of both polyclonal and monoclonal antibodies specific to TSG101 into cells during G₁ or S phase results in cell cycle arrest. Furthermore, overexpression of TSG101 leads to cell death, suggesting that the appropriate amount of TSG101 is critical for cell cycle progression. Taken together, these results suggest that neoplastic transformation caused by TSG101 deficiency may result from bypassing of the cell cycle checkpoints.

¹ Supported in part by NIH Grants CA58318 and EY05758 and the Alice McDermott endowment fund.

² To whom requests for reprints should be addressed, at Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245. Phone: (210) 567-7353; Fax: (210) 567-7377.

Received 3/ 5/98. Accepted 5/15/98.

This article has been cited by other articles:

				T. W. Young, D. G. Rosen, F. C. Mei, N. Li, J. Liu, X.-F. Wang, and X. Cheng Up-regulation of Tumor Susceptibility Gene 101 Conveys Poor Prognosis through Suppression of p21 Expression in Ovarian Cancer Clin. Cancer Res., July 1, 2007; 13(13): 3848 - 3854. [Abstract] [Full Text] [PDF]

				A. A. Bashirova, G. Bleiber, Y. Qi, H. Hutcheson, T. Yamashita, R. C. Johnson, J. Cheng, G. Alter, J. J. Goedert, S. Buchbinder, et al. Consistent Effects of TSG101 Genetic Variability on Multiple Outcomes of Exposure to Human Immunodeficiency Virus Type 1 J. Virol., July 15, 2006; 80(14): 6757 - 6763. [Abstract] [Full Text] [PDF]

				O. O. Olabisi, G. M. Mahon, E. V. Kostenko, Z. Liu, H. L. Ozer, and I. P. Whitehead Bcr interacts with components of the endosomal sorting complex required for transport-I and is required for epidermal growth factor receptor turnover. Cancer Res., June 15, 2006; 66(12): 6250 - 6257. [Abstract] [Full Text] [PDF]

				A. T. Agoston, P. Argani, S. Yegnasubramanian, A. M. De Marzo, M. A. Ansari-Lari, J. L. Hicks, N. E. Davidson, and W. G. Nelson Increased Protein Stability Causes DNA Methyltransferase 1 Dysregulation in Breast Cancer J. Biol. Chem., May 6, 2005; 280(18): 18302 - 18310. [Abstract] [Full Text] [PDF]

				M. J. Carstens, A. Krempler, A. A. Triplett, M. van Lohuizen, and K.-U. Wagner Cell Cycle Arrest and Cell Death Are Controlled by p53-dependent and p53-independent Mechanisms in Tsg101-deficient Cells J. Biol. Chem., August 20, 2004; 279(34): 35984 - 35994. [Abstract] [Full Text] [PDF]

				S. Burgdorf, P. Leister, and K. H. Scheidtmann TSG101 Interacts with Apoptosis-antagonizing Transcription Factor and Enhances Androgen Receptor-mediated Transcription by Promoting Its Monoubiquitination J. Biol. Chem., April 23, 2004; 279(17): 17524 - 17534. [Abstract] [Full Text] [PDF]

				P. Whitley, B. J. Reaves, M. Hashimoto, A. M. Riley, B. V. L. Potter, and G. D. Holman Identification of Mammalian Vps24p as an Effector of Phosphatidylinositol 3,5-Bisphosphate-dependent Endosome Compartmentalization J. Biol. Chem., October 3, 2003; 278(40): 38786 - 38795. [Abstract] [Full Text] [PDF]

				A. Goff, L. S. Ehrlich, S. N. Cohen, and C. A. Carter Tsg101 Control of Human Immunodeficiency Virus Type 1 Gag Trafficking and Release J. Virol., September 1, 2003; 77(17): 9173 - 9182. [Abstract] [Full Text] [PDF]

				Q. Lu, L. W. Hope, M. Brasch, C. Reinhard, and S. N. Cohen TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation PNAS, June 24, 2003; 100(13): 7626 - 7631. [Abstract] [Full Text] [PDF]

				K.-U. Wagner, A. Krempler, Y. Qi, K. Park, M. D. Henry, A. A. Triplett, G. Riedlinger, E. B. Rucker III, and L. Hennighausen Tsg101 Is Essential for Cell Growth, Proliferation, and Cell Survival of Embryonic and Adult Tissues Mol. Cell. Biol., January 1, 2003; 23(1): 150 - 162. [Abstract] [Full Text]

				A. Krempler, M. D. Henry, A. A. Triplett, and K.-U. Wagner Targeted Deletion of the Tsg101 Gene Results in Cell Cycle Arrest at G1/S and p53-independent Cell Death J. Biol. Chem., November 1, 2002; 277(45): 43216 - 43223. [Abstract] [Full Text] [PDF]

				G. H. Feng, C.-J. Lih, and S. N. Cohen TSG101 Protein Steady-State Level Is Regulated Posttranslationally by an Evolutionarily Conserved COOH-Terminal Sequence Cancer Res., March 1, 2000; 60(6): 1736 - 1741. [Abstract] [Full Text]

				N. Bishop and P. Woodman TSG101/Mammalian VPS23 and Mammalian VPS28 Interact Directly and Are Recruited to VPS4-induced Endosomes J. Biol. Chem., April 6, 2001; 276(15): 11735 - 11742. [Abstract] [Full Text] [PDF]

				L. VerPlank, F. Bouamr, T. J. LaGrassa, B. Agresta, A. Kikonyogo, J. Leis, and C. A. Carter Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55Gag PNAS, July 3, 2001; 98(14): 7724 - 7729. [Abstract] [Full Text] [PDF]