Even so, the mitotic mechanism underlying the disaggregation process remains unclear

Might this indicate an unrecognised structural link between the nucleus and the ER?

It also remains unclear why an NLS reduces aggregation—perhaps by bypassing ER entry. BiP’s access to these nuclear aggregates is equally perplexing.

How these aggregates enter the nucleus remains uncertain, given their size exceeds the nuclear pore limit and their surrounding membrane suggests an endoplasmic reticulum origin.

Misfolded proteins targeted to the endoplasmic reticulum unexpectedly form nuclear aggregates enclosed by a thin ER membrane. These aggregates are cleared following mitosis via CDK1 inactivation and BiP-mediated disaggregation.

elifesciences.org/articles/96675

Of course, active processes are at play, yet the forces driving cellular dynamics extend far beyond our current understanding. We still lack a unified theory capable of accounting for the full spectrum of cellular behaviors and dynamics.

Inevitably, we represent cells in ℝ², within clearly defined, finite boundaries, devoid of gravitational effects. We often treat proteins as discrete units, whose assembly we model as though it were a mechanical assembly line.

🔸️🔸️🔸️🔹️CRISPR studies show that knocking out certain dark proteins affects cell survival, suggesting some have functional roles.

🔸️🔸️🔸️AI tools like AlphaFold often struggle to predict their structure, as many lack well-folded domains

🔸️🔸️At times playing a essential role, at others may be transient or quickly degraded, many are abundant in cancer cells.

🔸️These proteins are typically small, often fewer than 100 amino acids + not well conserved across species

🔸️🔸️🔸️🔹️🔹️🔹️Science has been reduced to a corrosive environment, so consider carefully whether your contributions are helping to dismantle this fragile ecosystem or to preserve it.