Cyclin Cln3 is retained at the ER and released by the J chaperone Ydj1 in late G1 to trigger cell cycle entry

Abstract

G1 cyclin Cln3 plays a key role in linking cell growth and proliferation in budding yeast. It is generally assumed that Cln3, which is present throughout G1, accumulates passively in the nucleus until a threshold is reached to trigger cell cycle entry. We show here that Cln3 is retained bound to the ER in early G1 cells. ER retention requires binding of Cln3 to the cyclin-dependent kinase Cdc28, a fraction of which also associates to the ER. Cln3 contains a chaperone-regulatory Ji domain that counteracts Ydj1, a J chaperone essential for ER release and nuclear accumulation of Cln3 in late G1. Finally, Ydj1 is limiting for release of Cln3 and timely entry into the cell cycle. As protein synthesis and ribosome assembly rates compromise chaperone availability, we hypothesize that Ydj1 transmits growth capacity information to the cell cycle for setting efficient size/ploidy ratios.

We thank So` nia Rius and Isis Navarro for their technical assistance; Emilio Camafeita for mass spectrometry analysis; and Carl Mann, Noel Lowndes, Howard Riezman, and Elisabeth Craig for the gift of antibodies. We also thank Paul Nurse for helpful comments, and Jordi Torres and Mario Encinas for critically reading the manuscript. This work was funded by the Ministry of Education and Science of Spain, Fundacio´ La Caixa, and the European Union (FEDER). N.C. is a researcher of the Ramon y Cajal programme. E.V. received a fellowship from Generalitat de Catalunya.