Related Experiment Video

Updated: Jun 12, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Mitochondrial Hep27 is a c-Myb target gene that inhibits Mdm2 and stabilizes p53

Chad Deisenroth1, Aaron R Thorner, Takeharu Enomoto

  • 1University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, School of Medicine, Chapel Hill, NC, USA.

Molecular and Cellular Biology
|June 16, 2010
PubMed

Insights

Researchers discovered Hep27, a protein that moves from mitochondria to the nucleus. It binds to Mdm2, preventing the degradation of p53, a key tumor suppressor. This pathway impacts estrogen receptor-positive breast cancers.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • The tumor suppressor p53 is regulated by Mdm2, a key component of cellular stress response pathways.
  • Understanding Mdm2 regulation is crucial for defining cellular metabolism, apoptosis, and cell cycle control.
  • Identifying novel Mdm2 binding partners can elucidate new regulatory mechanisms.

Purpose of the Study:

  • To identify novel Mdm2 binding partners using large-scale immunoprecipitation.
  • To characterize the function and localization of identified binding partners.
  • To investigate the role of a novel Mdm2 binding partner, Hep27, in p53 regulation and its potential link to breast cancer.

Main Methods:

  • Large-scale immunoprecipitation of Mdm2 in U2OS osteosarcoma cells.
  • Analysis of Hep27 protein localization, including mitochondrial import and nuclear translocation.
  • Investigation of Hep27's interaction with Mdm2 and its effect on p53 degradation.
  • Assessment of Hep27's transcriptional regulation by c-Myb.
  • Correlation of Hep27 expression with estrogen receptor (ER) status in breast cancer gene expression data.

Main Results:

  • Hep27, a short-chain alcohol dehydrogenase/reductase (SDR) family member, was identified as an Mdm2 binding partner.
  • Hep27 contains a mitochondrial targeting signal, and mature Hep27 accumulates in the mitochondrial matrix.
  • A fraction of mitochondrial Hep27 translocates to the nucleus, binding Mdm2 and attenuating Mdm2-mediated p53 degradation.
  • Hep27 is transcriptionally regulated by c-Myb and is essential for c-Myb-induced p53 stabilization.
  • Hep27 expression correlates with ER status and p53 function in breast cancer, suggesting a link to estrogen receptor signaling.

Conclusions:

  • A novel mitochondria-to-nucleus signaling pathway involving c-Myb, Hep27, Mdm2, and p53 has been identified.
  • Hep27 acts as a crucial regulator of p53 stability by modulating Mdm2 activity.
  • This pathway may hold functional significance for estrogen receptor-positive breast cancers, offering potential therapeutic targets.

More Related Videos

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk113:15

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1

Published on: February 25, 2016

Related Concept Videos

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 daughter...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...