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Rab27b, member RAS oncogene family (Rab27b)
- Target
- Rab27b
- Molecular classification
- Small GTPase, Rab family protein, Enzyme (GTPase), Vesicle trafficking regulator
01
Overview
Rab27b is a member of the Rab family of small GTPases involved in the regulation of intracellular membrane trafficking, particularly exocytosis. It controls the number and secretion of platelet dense granules and is essential for regulated vesicle trafficking in several cell types including platelets, megakaryocytes, and some epithelial tissues. In cancer, Rab27b has been shown to promote myeloid malignancies by regulating NRAS palmitoylation and plasma membrane localization, which is essential for NRAS-mediated oncogenic signaling. High expression of Rab27b correlates with poor prognosis in acute myeloid leukemia and may also play a role in solid tumor metastasis. Rab27b interacts with effector proteins such as melanophilin and ZDHHC9, influencing both vesicular secretion and fundamental oncogenic signaling pathways, making it an emerging therapeutic target in oncology
- Other names
- Rab-27BRAB27BRas-related protein Rab-27b
02
Mechanism of action
Modulation of NRAS signaling by regulating its palmitoylation and membrane localization, affecting downstream pathways like RAF/MEK/ERK
03
Biological functions
Regulation of vesicle traffickingExocytosis of secretory lysosomes and dense granulesPlatelet dense granule secretionPalmitoylation and plasma membrane localization of NRASControl of exosome secretion
04
Disease associations
Cancer (notably acute myeloid leukemia, various solid tumors)Bleeding disorders (platelet dense granule deficiency)
05
Safety considerations
Potential risk of bleeding due to disruption of platelet dense granule secretionPossible immunological or secretory defects (redundancy with other Rab proteins varies by cell type)
06
Interacting drugs
None directly documented; MEK inhibitors are more efficacious in AMLs with high RAB27B expression but do not directly target Rab27b
07
Biomarkers
RAB27B expression (prognostic in AML—high expression associates with poor survival and sensitivity to MEK inhibitors)
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