DNAJC5 promotes hepatocellular carcinoma cells proliferation though regulating SKP2 mediated p27 degradation

Hailong Wang1, Jiayu Luo1, Xuesi Tian1

  • 1Center for Experimental Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang, Jiangxi, China.

Insights

DNAJC5 protein promotes hepatocellular carcinoma (HCC) growth by interacting with SKP2 to degrade p27. This discovery reveals a new oncogenic mechanism for DNAJC5 in HCC, impacting patient prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • DNAJC5 (DnaJ heat shock protein family member C5), also known as cysteine tandem protein (CSPα), is crucial for nerve tissue function.
  • The oncogenic role of DNAJC5 in cancer, particularly hepatocellular carcinoma (HCC), has not been previously established.

Purpose of the Study:

  • To investigate the potential oncogenic function of DNAJC5 in hepatocellular carcinoma (HCC).
  • To elucidate the molecular mechanism by which DNAJC5 contributes to HCC development and progression.

Main Methods:

  • Analysis of DNAJC5 protein expression in human HCC tissues.
  • Assessment of DNAJC5's effect on HCC cell proliferation and cell cycle.
  • Investigation of the interaction between DNAJC5, SKP2, and p27 using molecular assays.

Main Results:

  • DNAJC5 protein expression is elevated in HCC tissues and correlates with poor patient prognosis.
  • Overexpression of DNAJC5 enhances HCC cell proliferation by promoting cell cycle progression from G1 phase.
  • DNAJC5 interacts with SKP2, facilitating the degradation of p27 (a cyclin-dependent kinase inhibitor) and leading to decreased p27 protein levels.

Conclusions:

  • The DNAJC5-SKP2-p27 signaling pathway represents a novel mechanism for DNAJC5's oncogenic activity in HCC.
  • Targeting the DNAJC5-SKP2-p27 pathway may offer a therapeutic strategy for hepatocellular carcinoma.

Related Concept Videos

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...
5.3K
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...
4.9K
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...
7.1K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.9K
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.
37.4K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.1K