DENN domain-containing protein 2B (DENND2B)

DENN domain-containing protein 2B is a member of the DENN domain-containing protein family, functions as a guanine nucleotide exchange factor (GEF) for Rab13, Rab10, and RhoA, and localizes to the cell periphery to regulate actin dynamics, vesicular trafficking, and cell migration. It interacts with the effector MICAL-L2 and plays essential roles in cell morphological changes associated with invasiveness and metastasis in epithelial and cancer cells. Initially identified as a suppressor of tumorigenicity (ST5), different isoforms exert opposing influences on cancer cell behavior. DENND2B also inhibits primary cilia formation and regulates ciliary length via its activities on Rab and Rho GTPases, suggesting a broader role in cell signaling and structural dynamics. DENND2B is not a receptor or enzyme but a regulatory protein acting as a GEF for small GTPases essential in trafficking and cell structure. It functions as a regulator of vesicle delivery, actin remodeling, and cell polarity, and can promote epithelial cancer metastasis. Its role in suppressing or promoting cancer appears isoform-dependent, with full-length DENND2B promoting invasiveness and a truncated p70 isoform suppressing tumorigenicity. No direct drugs in clinical use currently target DENND2B, and biomarkers are not standardized for clinical application.

Other names

HTS1Suppression of tumorigenicity 5 protein (ST5)p126HeLa tumor suppression 1HeLa tumor suppressionDENN/MADD domain containing 2B

When targeted, would likely involve inhibition of GEF activity for Rab13 or Rab10, blocking cell migration/invasion and vesicular trafficking. Suppressing DENND2B may reduce metastatic potential and invasiveness of cancer cells.