Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1.

Growth factor independence 1 (Gfi1) is a transcriptional repressor essential for the function and development of many different hematopoietic lineages. The Gfi1 protein expression is regulated by the ubiquitin-proteasome system. In granulocytes, Gfi1 is rapidly degraded by the proteasome, while it is more stable in monocytes.

Diminished proteasomal degradation results in accumulation of Gfi1 protein in monocytes.

Gfi1 is a transcriptional repressor essential during myeloid differentiation. Gfi1-/- mice exhibit a block in myeloid differentiation resulting in the accumulation of an immature myelo-monocytic cell population and the complete absence of mature neutrophils. Even though mRNA levels of Gfi1 appear to be very low in monocytes, Gfi1 might play a role in the monocytic lineage as Gfi1-/- mice exhibit diminished monocyte-derived dendritic cells and disturbed cytokine production by macrophages in response to LPS.

The E3 ubiquitin-protein ligase Triad1 inhibits clonogenic growth of primary myeloid progenitor cells.

Protein ubiquitination plays important roles in a variety of basic cellular processes. Proteins are ubiquitinated by E2-E3 ubiquitin ligase complexes. Depending on the type of ubiquitin chain conjugated, proteins are either targeted for degradation by the proteasome or their activity is specifically altered.