Related Experiment Video

Updated: May 22, 2026

Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts
07:18

Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts

Published on: June 13, 2019

The SARAH Domain of RASSF1A and Its Tumor Suppressor Function

Claudia Dittfeld1, Antje M Richter, Katrin Steinmann

  • 1AWG Tumor Genetics of the Medical Faculty, Martin-Luther-University Halle-Wittenberg, 06108 Halle, Germany.

Molecular Biology International
|May 12, 2012
PubMed

Insights

The SARAH domain of RASSF1A is crucial for its tumor suppressor function. Deleting this domain in lung cancer cells still reduced growth but altered mitosis and increased apoptosis, indicating its regulatory role.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • The Ras association domain family 1A (RASSF1A) is a tumor suppressor.
  • RASSF1A contains a Sav-RASSF-Hpo (SARAH) domain involved in protein interactions.
  • The SARAH domain mediates interactions with hWW45 (dSAV) and MST1/2 (dHpo).

Purpose of the Study:

  • To investigate the role of the SARAH domain in RASSF1A's tumor suppressor activity.
  • To determine how SARAH domain deletion affects RASSF1A's interaction with MST1/2 and its cellular functions.

Main Methods:

  • Demonstrated interaction between RASSF1A/RASSF1C and MST1/2, dependent on the SARAH domain.
  • Compared the effects of full-length RASSF1A and SARAH domain-deleted RASSF1A on lung cancer cell line A549 growth, including anchorage-independent growth.
  • Analyzed mitotic rates, metaphase abnormalities, apoptosis, and mitotic spindle formation in cells expressing different RASSF1A forms.

Main Results:

  • SARAH domain-deleted RASSF1A retained growth-reducing effects and inhibited anchorage-independent growth in A549 cells.
  • Deletion of the SARAH domain led to reduced mitotic rates and increased abnormal metaphases (P < 0.001).
  • A significantly increased rate of apoptosis (P = 0.006) was observed with SARAH domain-deleted RASSF1A, and mitotic spindle formation was altered.

Conclusions:

  • The SARAH domain is critical for the proper regulation of RASSF1A's tumor suppressor functions.
  • While RASSF1A lacking the SARAH domain retains some growth inhibitory properties, its absence disrupts normal mitotic processes and promotes apoptosis.
  • These findings highlight the specific importance of the SARAH domain in mediating RASSF1A's effects on cell division and survival.

More Related Videos

Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas09:21

Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas

Published on: September 13, 2019

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 superfamily...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...