The p75NTR-interacting protein SC1 inhibits cell cycle progression by transcriptional repression of cyclin E

Abstract

Schwann cell factor 1 (SC1), a p75 neurotrophin receptor–interacting protein, is a member of the positive regulatory/suppressor of variegation, enhancer of zeste, trithorax (PR/SET) domain-containing zinc finger protein family, and it has been shown to be regulated by serum and neurotrophins. SC1 shows a differential cytoplasmic and nuclear distribution, and its presence in the nucleus correlates strongly with the absence of bromodeoxyuridine (BrdU) in these nuclei. Here, we investigated potential transcriptional activities of SC1 and analyzed the function of its various domains. We show that SC1 acts as a transcriptional repressor when it is tethered to Gal4 DNA-binding domain. The repressive activity requires a trichostatin A–sensitive histone deacetylase (HDAC) activity, and SC1 is found in a complex with HDACs 1, 2, and 3. Transcriptional repression exerted by SC1 requires the presence of its zinc finger domains and the PR domain. Additionally, these two domains are involved in the efficient block of BrdU incorporation by SC1. The zinc finger domains are also necessary to direct SC1's nuclear localization. Lastly, SC1 represses the promoter of a promitotic gene, cyclin E, suggesting a mechanism for how growth arrest is regulated by SC1.

Prdm12 Is Induced by Retinoic Acid and Exhibits Anti-proliferative Properties through the Cell Cycle Modulation of P19 Embryonic Carcinoma Cells

“…4). It has been reported that the PR and ZF domains are required for Prdm4 to inhibit the cell cycle through the transcriptional repression of cyclin E (Chittka et al, 2004). Therefore, the properties of Prdm12 we demonstrated are similar to other Prdms.…”

p75 Neurotrophin Receptor Expression Defines a Population of BDNF-Responsive Neurogenic Precursor Cells

“…We propose that activation of p75 NTR on SVZ precursors favors neuroblast generation, a function consistent with the ability of p75 NTR to promote cell cycle progression and terminal differentiation in other systems (Cattaneo and McKay, 1990;Seidl et al, 1998;Lachyankar et al, 2003). For example, neurotrophin-stimulated signaling has been shown to act through downstream p75 NTR -interacting proteins, such as Schwann cell factor-1, to promote withdrawal from the cell cycle (Chittka and Chao, 1999;Chittka et al, 2004) and facilitate the expression of differentiation-promoting genes (Ito et al, 2003).…”

Proteolytic processing of the p75 neurotrophin receptor: A prerequisite for signalling?

“…[76]). A number of intracellular proteins that control various aspects of the cell cycle, including Schwann cell factor-1 (Sc-1), brain-expressed X-linked 1 (Bex1) and melanoma antigen gene (MAGE) proteins, interact with the ICD of p75 NTR , and are found in the nucleus after ligand activation of p75 NTR [79][80][81]. The p75 NTR -interacting protein, NRIF, has been found in the nucleus with the ICD of p75 NTR following RIP [17], and RIP is required for p75 NTR -dependent Amyloid b-induced neurogenesis [82].…”