Gm. Souza et al., Starvation promotes Dictyostelium development by relieving PufA inhibitionof PKA translation through the YakA kinase pathway, DEVELOPMENT, 126(14), 1999, pp. 3263-3274
When nutrients are depleted, Dictyostelium cells undergo cell cycle arrest
and initiate a developmental program that ensures survival. The YakA protei
n kinase governs this transition by regulating the cell cycle, repressing g
rowth-phase genes and inducing developmental genes. YakA mutants have a sho
rtened cell cycle and do not initiate development. A suppressor of yakA tha
t reverses most of the developmental defects of yakA cells, but none of the
ir growth defects was identified. The inactivated gene, pufA, encodes a mem
ber of the Puf protein family of translational regulators, Upon starvation,
pufA(-) cells develop precociously and overexpress developmentally importa
nt proteins, including the catalytic subunit of cAMP-dependent protein kina
se, PKA-C, Gel mobility-shift assays using a 200-base segment of PKA-C's mR
NA as a probe reveals a complex with wild-type cell extracts, but not with
pufA- cell extracts, suggesting the presence of a potential PufA recognitio
n element in the PKA-C mRNA, PKA-C protein levels are low at the times of d
evelopment when this complex is detectable, whereas when the complex is und
etectable PKA-C levels are high. There is also an inverse relationship betw
een PufA and PKA-C protein Levels at;all times of development in every muta
nt tested. Furthermore, expression of the putative PufA recognition element
s in wild-type cells causes precocious aggregation and PKA-C overexpression
, phenocopying a pufA mutation. Finally, YakA function is required for the
decline of PufA protein and mRNA levels in the first 4 hours of development
. We propose that PufA is a translational regulator that directly controls
PKA-C synthesis and that YakA regulates the initiation of development by in
hibiting the expression of PufA, Our work also suggests that Puf protein tr
anslational regulation evolved prior to the radiation of metazoan species.