Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis.

Kaposi sarcoma is a tumor consisting of Kaposi sarcoma herpesvirus (KSHV)-infected tumor cells that express endothelial cell (EC) markers and viral genes like v-cyclin, vFLIP, and LANA. Despite a strong link between KSHV infection and certain neoplasms, de novo virus infection of human primary cells does not readily lead to cellular transformation. We have studied the consequences of expression of v-cyclin in primary and immortalized human dermal microvascular ECs.

Characterization of the Rab8-specific membrane traffic route linked to protrusion formation.

Rab8 has a drastic effect on cell shape, but the membrane trafficking route it regulates is poorly defined. Here, we show that endogenous and ectopically expressed Rab8 is associated with macropinosomes generated at ruffling membrane domains. These macropinosomes fuse or transform into tubules that move toward the cell center, from where they are recycled back to the leading edge.

The C-terminal end of R-Ras contains a focal adhesion targeting signal.

R-Ras promotes cell adhesion and activation of integrins through a process that is yet unknown. We show here that active R-Ras (38V) promotes the formation of focal adhesions and a spread cell shape. By contrast, the dominant-negative mutant of R-Ras (43N) reduces the number of focal adhesions, leading to the formation of refractile cells.

A Rab8-specific GDP/GTP exchange factor is involved in actin remodeling and polarized membrane transport.

The mechanisms mediating polarized delivery of vesicles to cell surface domains are poorly understood in animal cells. We have previously shown that expression of Rab8 promotes the formation of new cell surface domains through reorganization of actin and microtubules. To unravel the function of Rab8, we used the yeast two-hybrid system to search for potential Rab8-specific activators.