trnp: A Conserved Mammalian Gene Encoding a Nuclear Protein That Accelerates Cell-Cycle Progression

Abstract

We herein describe a novel protein encoded by a single exon in a single-copy conserved mammalian gene. This protein, termed TMF regulated nuclear protein (TRNP), was identified in a yeast "two-hybrid" screen in which the "BC box" containing protein-TMF/ARA160 served as a bait. TRNP is a basic protein which accumulates in an insoluble nuclear fraction in mammalian cells. It is 227 aa long in humans and chimps and 223 aa long in mice. Enforced expression of TRNP in cells that do not express this protein significantly increased their proliferation rate by enhancing their cell-cycle progression from the G0/G1 to the S phase. Like another proliferation promoting factor, Stat3, TRNP was directed to proteasomal degradation by TMF/ ARA160. Thus, the trnp gene encodes a novel mammalian conserved nuclear protein that can accelerate cellcycle progression and is regulated by TMF/ARA160.

TMF/ARA160 downregulates proangiogenic genes and attenuates the progression of PC3 xenografts

“…The cells were transfected using the LipofectAMINE reagent (Invitrogen, Paisley, UK). Each transfection was performed by mixing 10 μg DNA, pcDNA3 empty vector, or pcDNA3‐HA‐TMF or pcDNA3‐HA‐TMF‐ΔBC (as described previously) with 25 μL of LipofectAMINE and 1 mL serum‐free Opti‐MEM (Gibco, Invitrogen, Paisley, UK) medium as described before 9. After 24 hr, cells were trypsinized (Gibco, Invitrogen, Paisley, UK) and replated at 2 different dilutions (20×, 40×), in quadruplicates in 10‐cm dishes.…”

“…TMF was originally identified as a TATA element modulatory factor6 that binds to the androgen receptor and in PC3 prostate carcinoma cells potentiates the transcription‐inducing activity of the androgen receptor in a ligand‐dependent manner 7. Finally, TMF was shown to become dispersed in the cytoplasm and to mediate the delivery of Stat3 and TRNP to proteasomal degradation under conditions of growth factor deprivation 8, 9. The TMF‐directed ubiquitination of Stat3 is mediated by a “BC box” element, which resides in the N‐terminal portion of the protein and enables its association with an E3 ubiquitin ligase complex 8…”

The Outer Subventricular Zone and Primate-Specific Cortical Complexification

“…Likewise, a transient expansion of BPs subsequent to CyclinD1/Cdk4 overexpression increases the cortical thickness of the late embryonic brain (Lange et al, 2009;Nonaka-Kinoshita et al, 2013). Knockdown of Trnp1, which regulates proliferation (Volpe et al, 2006), prolongs BPs in a proliferative mode, thereby inducing a thick SVZ and a radial expansion of the cortex . Further, p27 KIP1 mutants exhibit excess upper-layer neurons as a consequence of selective G1 shortening in the BP pool (Mairet-Coello et al, 2012).…”

Identification of differentially expressed lncRNAs involved in transient regeneration of the neonatal C57BL/6J mouse heart by next-generation high-throughput RNA sequencing

“…For instance, the lncRNA fantom3_B230352I09, which was downregulated in P7, was co-expressed with 17 coding genes, most of which were related to apoptosis, cell growth, regulation of the cell cycle and cell proliferation. As another example, the Trnp1 gene [44] has been reported to accelerate cell cycle progression and the Pim3 gene [45] has a cardio-protective effect through the process of anti-apoptosis. Igfbp3 is a downstream target of Wnt signaling pathway and participates in the regulation of adult cardiac progenitor cell regeneration [46].…”