Nup153 is a specialized protein and a member of a group known as nucleoporins, which are dedicated to tasks involving the cell’s nucleus. The nucleus acts as the command center that houses the cell’s genetic blueprint, DNA. Nup153 performs several distinct jobs related to the nucleus, contributing to cellular order and function. Its roles include managing how materials move within the cell and how genetic information is used.
The Nuclear Pore Complex
The cell’s nucleus is enclosed by a double membrane called the nuclear envelope, separating the genetic material from the surrounding cytoplasm. Communication and transport between these compartments are controlled by channels known as Nuclear Pore Complexes (NPCs). These structures are embedded across the nuclear envelope, acting as the sole gateways for molecules to pass through.
Functioning like regulated security checkpoints, NPCs ensure only approved molecules can enter or exit the nucleus. Each NPC is a large machine built from approximately 30 different proteins called nucleoporins. These components assemble into a complex structure with a central channel and filaments that extend into both the cytoplasm and the nucleus, allowing the NPC to handle a high volume of traffic.
Nup153’s Specific Location and Structure
Within the Nuclear Pore Complex, Nup153 occupies a strategic position as a component of the “nuclear basket,” a structure extending from the pore into the nucleoplasm. Its placement on the nuclear side means Nup153 is one of the first proteins molecules encounter when exiting the nucleus and one of the last upon entry. This location allows it to play a direct role in the final stages of nuclear import and the initial steps of export.
The structure of Nup153 has three main parts. An N-terminal region helps anchor it to the NPC and the nuclear envelope. A central domain contains “zinc fingers,” which are structures capable of binding to DNA. The C-terminal end is a long, flexible tail characterized by repeating sequences of phenylalanine and glycine, known as “FG repeats,” which extends into the pore’s central channel to form a selective barrier.
Regulating Nuclear Transport
Nup153 plays a central role in managing molecular traffic through the nuclear pore. Its C-terminal tail, rich in FG repeats, creates a gel-like meshwork within the pore’s central channel that acts as a selective barrier. For large cargo to cross this barrier, it must be escorted by transport receptor proteins, like importins for entry and exportins for exit.
These receptors interact with the FG repeats of Nup153, which allows the receptor and its cargo to move through the pore. Nup153 is a primary binding partner for importin β, a receptor for bringing proteins into the nucleus.
Nup153’s involvement also extends to the export of various types of RNA molecules, including messenger RNA (mRNA) and ribosomal RNA (rRNA). Studies show that blocking Nup153 can halt the export of these molecules to the cytoplasm, suggesting it helps guide them through the export channel.
Role in Gene Expression and Cell Division
Beyond transport, Nup153 is involved in regulating gene activity. The protein’s zinc-finger domain allows it to bind to chromatin, the condensed structure of DNA and proteins in the nucleus. By attaching to specific regions of the genome near active genes, Nup153 can influence whether these genes are turned on or off. In some contexts, it helps recruit other regulatory proteins to gene sites, promoting an open chromatin environment that facilitates transcription.
Nup153 also has a role during mitosis, the process of cell division. When a cell divides, the nuclear envelope breaks down, and the nuclear pore complexes disassemble. As two new daughter cells form, their nuclear envelopes must be reassembled. Nup153 is involved in this reconstruction and is required for the formation of new NPCs. This role is controlled by chemical modifications to the protein that facilitate the disassembly and subsequent reassembly of the pore structure.
Connection to Human Health and Disease
Disruption of Nup153’s functions is linked to health issues like viral infections and cancer. For some viruses to replicate, they must deliver their genetic material into the host cell’s nucleus. The human immunodeficiency virus (HIV), for example, must traverse the nuclear pore to establish infection. The HIV capsid, the protein shell containing the viral genome, interacts with Nup153 to mediate its passage through the nuclear basket and into the nucleus.
Alterations in Nup153 levels or function are also observed in various types of cancer. Because Nup153 is involved in nuclear transport and gene regulation, its misregulation can disrupt cell growth and division. For example, elevated levels of Nup153 have been found in hepatocellular carcinoma, where it promotes cell proliferation. In other cancers, mutations can interfere with the transport of tumor-suppressor proteins, contributing to uncontrolled cell growth.