Proteomics of yeast telomerase identified Cdc48-Npl4-Ufd1 and Ufd4 as regulators of Est1 and telomere length

• DOI: 10.1038/ncomms9290
• Publication Date: 2015-09-14T09:51:17Z
• Authors: Kah-Wai Lin; Karin R. McDonald; Amanda J. Guise; Angela Chan; Ileana M. Cristea; Virginia A. Zakian
• Keywords: Telomere-binding protein; Telomerase RNA component

Abstract Almost 400 genes affect yeast telomere length, including Est1 , which is critical for recruitment and activation of telomerase. Here we use mass spectrometry to identify novel telomerase regulators by their co-purification with the holoenzyme. In addition all known subunits, over 100 proteins are associated, three subunits essential Cdc48-Npl4-Ufd1 complex as well E3 ubiquitin ligases. The Cdc48 evolutionarily conserved targets ubiquitinated degradation. levels ∼40-fold higher in cells reduced Cdc48, yet, paradoxically, telomeres shorter. Furthermore, its cell cycle-regulated abundance lost Cdc48-deficient cells. Deletion telomerase-associated ligase, Ufd4, cdc48-3 further increases but suppresses length phenotype single mutant. These data argue that, concert regulates controlling level activity Est1.