What is Nuclear Family?

Nuclear proteins like transcription factors and ribosomal proteins are synthesized in the cytoplasm and have to be transported into the nucleus to fulfill their functions. The transport of proteins >20-60 kDa through the nuclear pore complex (NPC) into the nucleus is an active, energy-requiring process. Transport substrates are recognized by their transport proteins via certain signals. The best-characterized protein import pathway is the 'classical' nuclear localization signal-dependent pathway with importin alpha and beta carrying the substrate to the NPC. The transport of the importin-substrate complex into the nucleus is regulated by the small GTPase Ran/TC4.

Nuclear Family is divided into 2 main classes including Lysine demethylase 4C (KDM4C) and PEST containing nuclear protein (PCNP).

--Lysine demethylase 4C (KDM4C)

Lysine demethylase 4C (KDM4C) is a nuclear protein that is essential for histone modification and acts as an important regulator of several transcription factors. KDM4C may play a critical role in regulating mitochondria, which is related to a protective effect on maintaining cell survival in AKI.

--PEST containing nuclear protein (PCNP) 

PEST containing nuclear protein (PCNP), one of the nuclear proteins is demonstrated as a tumor suppressor in a neuroblastoma cancer model and tumor promoter in lung adenocarcinoma cancer model. It has many unique properties like ubiquitination by NIRF, co-localization with NIRF in nucleus and tumor progression. PCNP is ubiquitinated by ring finger protein NIRF in E3 ligase manner and as modulator of MAPK and PI3K/AKT/mTOR signaling pathways. PCNP linked DNA damage response, post translational modifications, and transportation to address initiation, prognosis, and resistance of tumor cells in terms of cell cycle regulation, transcription and apoptosis. Hence, PCNP as a novel target in cancer diagnosis and treatment.

Figure 1 Platelet-derived growth factors from breast cancer or neuroblastoma stimulate the platelet-derived

growth factor (PDGF) receptors and initiate immune and tumorigenesis response

Figure 2 Ubiquitination of PEST containing nuclear protein (PEST) by

NIRF (Np95/ICBP90‐like RING finger protein) in the nuclear core of the cell

Nuclear Family, the major targets for drug discovery, provides a new research idea for drug intervention therapy of cancers.