Related Experiment Video

Updated: Jul 26, 2025

Author Spotlight: Integrating BRET-Based Assays and Rare Mutation Analysis to Decipher RAF Kinase Regulation in Live Cells
06:44

Author Spotlight: Integrating BRET-Based Assays and Rare Mutation Analysis to Decipher RAF Kinase Regulation in Live Cells

Published on: March 1, 2024

1.1K

RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia

Jian-Gang Ren1,2,3, Bowen Xing2,3, Kaosheng Lv2,3,4

  • 1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.

The Journal of Clinical Investigation
|June 15, 2023
PubMed

Insights

RAB27B protein regulates NRAS palmitoylation and cell membrane trafficking, crucial for RAS-driven cancers like acute myeloid leukemia (AML). Its depletion inhibits cancer growth and impacts therapeutic strategies.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Trafficking

Background:

  • RAS mutations are key drivers in many cancers.
  • RAS protein function depends on membrane association via lipid modifications.
  • Dysregulated RAS signaling contributes to myeloid malignancies.

Purpose of the Study:

  • To investigate the role of RAB27B in NRAS protein regulation and cancer development.
  • To explore RAB27B as a potential therapeutic target in RAS-driven cancers.

Main Methods:

  • Proteomic analysis to identify RAB27B in myeloid malignancies.
  • Cell line experiments assessing RAB27B depletion effects on NRAS and cell growth.
  • In vivo studies in mice to evaluate Rab27b deficiency in leukemia models.
  • Mechanistic studies involving protein interactions and signaling pathway analysis.

Main Results:

  • RAB27B controls NRAS palmitoylation and plasma membrane trafficking.
  • RAB27B is upregulated in CBL- or JAK2-mutated myeloid malignancies and correlates with poor AML prognosis.
  • RAB27B depletion inhibits growth of NRAS-mutant cells and reduces leukemia development in vivo.
  • RAB27B interacts with ZDHHC9, regulating NRAS palmitoylation and downstream ERK signaling.
  • RAB27B depletion inhibits oncogenic NRAS signaling and growth in human AMLs.
  • RAB27B expression correlates with MEK inhibitor sensitivity in AML.

Conclusions:

  • RAB27B is a critical regulator of NRAS posttranslational modification and trafficking.
  • RAB27B represents a potential therapeutic target for RAS-driven cancers, particularly AML.
  • Targeting RAB27B may offer new strategies for treating acute myeloid leukemia.
Keywords:
CancerCell BiologyHematologySignal transduction

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:39

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

182
Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.1K

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.3K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.7K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
4.0K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.7K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K