Palmitoylation by ZDHHC family members regulate B-cell lymphoma growth.

The ZDHHC palmitoyl transferase family consists of 24 members, of which several have been linked to the development of cancer. We previously showed that inhibition of ZDHHC11 decreased growth of several B-cell lymphoma subtypes. In this study, we evaluated the effect of protein palmitoylation on the proteome in general and investigated expression and function of ZDHHC family members in a panel of Burkitt, Hodgkin and diffuse large B-cell lymphoma cell lines. Proteomic analysis of Burkitt lymphoma cells treated with the general palmitoylation inhibitor 2-bromopalmitate (2-BP) revealed 1089 differentially expressed proteins of which 124 were involved in cell cycle and apoptosis related gene ontologies. In line with this, 2-BP treatment resulted in an increased percentage of apoptotic cells in all three lymphoma subtypes. To allow a further selection of the most relevant family members of ZDHHC palmitoyl transferases, we studied expression patterns and assessed the dependency. The combined analyses revealed potential roles for ZDHHC11 and ZDHHC18 in the observed phenotype. Knockdown of ZDHHC18 in four Burkitt lymphoma cell lines revealed a decreased cell viability. This is the first study showing a critical role for palmitoylation in controlling growth of B-cell lymphoma. Moreover, we provide evidence that next to the previously identified ZDHHC11, ZDHHC18 is also crucial for B-cell lymphoma growth expanding the potential functional role for ZDHHC family members in lymphomagenesis.