Sirtuin interacts with many regulatory proteins involved in energy homeostasis. We investigated the functional roles of Sir2D during the early Dictyosteliumdevelopment upon starvation. We found that the ectopic expression of Sir2D accelerated the development and upregulated the adenylate cyclase A (aca) mRNA expression at 2, 4 and 6 h after starvation. RNAi-mediated Sir2D knockdown cells was generated and found that the development was delayed, and aca expression was decreased at 4 h after starvation. Sir2D expression restored the developmental impairment of Sir2D knockdown cells. The induction of aca upon starvation starts with the transcriptional activation of MybB. The ectopic expression of MybB accelerated the development and increased the expression of aca at 2 and 4 h after starvation but could not restore the phenotype of Sir2D knockdown cells. Thus, Sir2D is necessary for the full induction of aca at 4 h by MybB. MybB was co-immunoprecipitated with Sir2D, suggesting the interaction between MybB and Sir2D. The result suggests that Sir2D regulates the aca expression through the interaction with a transcription factor MybB at the early Dictyosteliumdevelopment upon starvation.