We recently reported that functional loss of p53 altered the responses of human HCT116 colon cancer cells to apoptosis triggers. To examine the molecular basis underlying the differential responses to drug treatment in the cancer cells, we performed a proteomic analysis in order to compare the protein expressions between human colon cancer cells with and those without p53 (p53(+/+) and p53(-/-)) respectively. We identified two isoelectric variants of the chaperonin-containing tail-less complex polypeptide-1 gamma subunit (TCP-1γ) from the cells, and confirmed that the two isoelectric variants were phosphorylated at tyrosine residue(s). The p53(-/-) cells had higher protein concentration of the more acidic variant of TCP-1γ compared to their p53(+/+) counterparts. Moreover, TCP-1γ was found to be co-localized with centrosome. Our results implicate a novel cell signaling loop in HCt116 cells involving p53 and TCP1-γ phosphorylation, which may be related to regulation and action of centrosomes.