TATA-binding protein-like protein (TLP/TRF2/TLF) negatively regulates cell cycle progression and is required for the stress-mediated G(2) checkpoint.

Molecular and Cellular Biology
Miho ShimadaTaka-aki Tamura

Abstract

The TATA-binding protein (TBP) is a universal transcription factor required for all of the eukaryotic RNA polymerases. In addition to TBP, metazoans commonly express a distantly TBP-related protein referred to as TBP-like protein (TLP/TRF2/TLF). Although the function of TLP in transcriptional regulation is not clear, it is known that TLP is required for embryogenesis and spermiogenesis. In the present study, we investigated the cellular functions of TLP by using TLP knockout chicken DT40 cells. TLP was found to be dispensable for cell growth. Unexpectedly, TLP-null cells exhibited a 20% elevated cell cycle progression rate that was attributed to shortening of the G(2) phase. This indicates that TLP functions as a negative regulator of cell growth. Moreover, we found that TLP mainly existed in the cytoplasm and was translocated to the nucleus restrictedly at the G(2) phase. Ectopic expression of nuclear localization signal-carrying TLP resulted in an increase (1.5-fold) in the proportion of cells remaining in the G(2)/M phase and apoptotic state. Notably, TLP-null cells showed an insufficient G(2) checkpoint when the cells were exposed to stresses such as UV light and methyl methanesulfonate, and the population of apoptotic cell...Continue Reading

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Citations

Jul 23, 2004·Molecular Biology of the Cell·Philippe Kieffer-KwonIrwin Davidson
Oct 24, 2007·Molecular and Cellular Biology·Stephanie D BushJames L Manley
Jun 19, 2013·Annual Review of Microbiology·Kimberly B Decker, Deborah M Hinton
Jun 11, 2004·Médecine sciences : M/S·Irwin DavidsonStéphane Viville
Nov 18, 2006·Biochemical and Biophysical Research Communications·Yuji TanakaTaka-aki Tamura
May 4, 2016·Stem Cell Research & Therapy·Ieva BruzauskaiteEiva Bernotiene
Oct 4, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Momoko IsogaiTaka-Aki Tamura
Feb 17, 2006·Doklady. Biochemistry and Biophysics·D V KopytovaS G Georgieva
Dec 13, 2006·American Journal of Human Genetics·Paul N ValdmanisGuy A Rouleau

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