Related Experiment Video

Updated: Jun 2, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

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

Published on: July 17, 2019

The Cdc14B phosphatase displays oncogenic activity mediated by the Ras-Mek signaling pathway

Massimo Chiesa1, María Guillamot, María José Bueno

  • 1Spanish National Cancer Research Center, Madrid, Spain.

Cell Cycle (Georgetown, Tex.)
|April 20, 2011
PubMed

Insights

Mammalian Cdc14B phosphatase, unlike Cdc14A, drives malignant transformation by disrupting actin organization and activating the Ras-MAP kinase pathway. This oncogenic activity highlights Cdc14B

Area of Science:

  • Cell Biology
  • Biochemistry
  • Oncology

Background:

  • Vertebrate Cdc14 phosphatases (Cdc14A and Cdc14B) have unclear roles in cell cycle progression.
  • Cdc14's function in yeast mitotic exit is established, but its mammalian counterparts' relevance is poorly understood.

Purpose of the Study:

  • Investigate the functional relevance of mammalian Cdc14A and Cdc14B.
  • Determine the oncogenic potential of Cdc14B and its underlying molecular mechanisms.

Main Methods:

  • Overexpression of Cdc14A and Cdc14B in murine fibroblasts.
  • Analysis of cell morphology, cytoskeletal organization (F-actin, vinculin adhesions), and anchorage-independent growth.
  • In vivo tumor formation assays.
  • Transcriptional profiling and pharmacologic inhibition of the Ras-Mek pathway.

Main Results:

  • Cdc14B overexpression, not Cdc14A, induced malignant transformation and morphological changes in fibroblasts.
  • Cdc14B disrupted F-actin organization and vinculin adhesions in a phosphatase-dependent manner.
  • Cdc14B-overexpressing cells showed anchorage-independent growth and formed tumors in vivo, mimicking Ras oncogene effects.
  • Ras-MAP kinase pathway inhibition rescued Cdc14B-induced defects.

Conclusions:

  • Mammalian Cdc14B, unlike Cdc14A, possesses oncogenic activity.
  • Cdc14B transforms cells by disrupting cytoskeletal organization and activating the Ras-MAP kinase pathway.
  • Cdc14B represents a novel phosphatase with oncogenic potential, with the Ras-MAP kinase pathway as a key effector.

More Related Videos

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells06:44

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells

Published on: March 1, 2024

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

Related Concept Videos

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...
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 superfamily...
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:
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
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 rapamycin-insensitive companion...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...